1 Introduction

The objective of this notebook is to characterize the transcriptional signature associated with time at room temperature (RT) until cryopreservation in Peripheral Blood Mononuclear Cells (PBMC). We hypothesize that, as we are extracting blood cells from its physiological niche (~37ºC) and placing them at RT (~21ºC), they will express a transcriptional signature that allows them to cope with the change in temperature.

2 Pre-processing

2.1 Package loading

library(scater)
library(scran)
library(Seurat)
library(ggpubr)
library(biomaRt)
library(org.Hs.eg.db)
library(AnnotationDbi)
library(GOplot)
library(GOstats)
library(topGO)
library(ggrepel)
library(ggridges)
library(viridis)
library(pheatmap)
library(readxl)
library(tidyverse)

2.2 Source script with functions

source("bin/utils.R")

2.3 Load data

We dispose of a demultiplexed, filtered, normalized and annotated Seurat object that contains the transcriptome and metadata of >10,000 PBMC from two donors (male/female) that were kept at varying times at RT (0h, 2h, 8h, 24h, 48h).

pbmc <- readRDS("results/R_objects/10X_pbmc_Seurat_clustered.RDS")
pbmc <- subset(pbmc, subset = condition %in% c("0h", "2h", "8h", "24h_RT", "48h_RT"))
pbmc$time <- factor(pbmc$condition, levels = c("0h", "2h", "8h", "24h_RT", "48h_RT"))
levels(pbmc$time) <-  c("0h", "2h", "8h", "24h", "48h")
Idents(pbmc) <- "cell_type"
DimPlot(pbmc)

3 Transcriptional signature

To find the transcriptional signature associated with time, we will conduct a differential expression analysis between time-biased and time-unbiased cells. Such distinction is based on our previous results, which show that cells that are kept >2h at RT prior to cryopreservation possess altered transcriptional landscapes in comparison to those left for <=2h.

We will opt to use a wilcoxon test. Despite the fact that there are recent methods that are tailored to scRNA-seq DE, recent benchmarking suggest that (1) wilcoxon test is still among the best-performing tools and (2) with scran normalization there is no need for tailored methods.

First, let us assess the differential expression analysis for all cell types together:

pbmc$is_biased <- ifelse(pbmc$time %in% c("0h", "2h"), "unbiased", "biased")
Idents(pbmc) <- "is_biased"
dea_general <- FindMarkers(pbmc, ident.1 = "biased", test.use = "wilcox")
dea_general <- dea_general %>%
  rownames_to_column(var = "gene") %>% 
  dplyr::mutate(is_significant = ifelse(p_val_adj < 0.001, TRUE, FALSE))
genes <- rownames(pbmc[["RNA"]]@data)
avg_expr <- rowMeans(as.matrix(pbmc[["RNA"]]@data))
log2_fc <- apply(as.matrix(pbmc[["RNA"]]@data), 1, function(x) {
  mean_unbiased <- mean(x[pbmc$is_biased == "unbiased"]) + 1
  mean_biased <- mean(x[pbmc$is_biased == "biased"]) + 1
  log2(mean_biased / mean_unbiased)
})
is_significant <- ifelse(genes %in% dea_general$gene[dea_general$is_significant], TRUE, FALSE)
dea_all <- data.frame(
  gene = genes, 
  average_expression = avg_expr, 
  log2_fc = log2_fc,
  is_significant = is_significant
)
subset_sig <- dplyr::filter(dea_all, is_significant & log(average_expression + 1) > 0.5 & abs(log2_fc) > 0.2)
top_up <- as.character(subset_sig$gene[subset_sig$log2_fc > 0])
top_down <- subset_sig %>% 
  dplyr::arrange(log2_fc)
top_down <- as.character(top_down$gene[1:10])
subset_sig <- dplyr::filter(subset_sig, gene %in% c(top_up, top_down))
ma_plot_all <- dea_all %>% 
  ggplot(aes(log(average_expression + 1), log2_fc, color = is_significant)) +
    geom_point(size = 0.85, alpha = 0.6) +
    geom_smooth(method = "loess", color = "darkblue") +
    geom_hline(yintercept = 0, color = "black", linetype = "dashed") +
    scale_color_manual(values = c("gray78", "green4"), labels = c("sig", "no sig")) +
    labs(x = "log (Average Expression)", y = "log (biased / unbiased)", color = "") +
    theme_classic2() +
    theme(axis.title = element_text(size = 11),
          legend.text = element_text(size = 11),
          plot.title = element_text(hjust = 0.5, face = "bold"))
ma_plot_all +    
  geom_text_repel(data = subset_sig, aes(label = gene), color = "black") 

# saveRDS(ma_plot_all, "results/R_objects/ggplots/ma_plot_all_types_pbmc.rds")
dea_all <- arrange(dea_all, desc(abs(log2_fc)))
DT::datatable(dea_all)
# saveRDS(dea_general$gene, "results/R_objects/cold_shock_signature.rds")
# saveRDS(dea_general$gene[dea_general$avg_logFC > 0], "results/R_objects/cold_shock_signature_up.rds")
# saveRDS(dea_all, "results/R_objects/dea_results_pbmc.rds")

Overall, we detected a total of 236 differential expressed genes (DEG), 61 of which were upregulated and 175 were downregulated.

Important: note that some analysis were recomputed in the directory “4-REVISION” to answer concerns raised by reviewer 2.

Let’s visualize the same information with a dot plot:

expr_matr <- scale(as.matrix(pbmc[["RNA"]]@data), TRUE, TRUE)
meta_df <- data.frame(
  time = c(), 
  gene = c(),
  expression = c(), 
  fraction_expr = c()
)
times <- c("0h", "2h", "8h", "24h", "48h")
genes <- c(top_down, top_up)
for (t in times) {
  for (g in genes) {
    cells <- colnames(pbmc)[pbmc$time == t]
    expr <- mean(expr_matr[g, cells])
    frc_expr <- mean(as.numeric(pbmc[["RNA"]]@counts[g, cells]) != 0) 
    current_df <- data.frame(
      gene = g, 
      time = t, 
      expression = expr, 
      fraction_expr = frc_expr
    )
    meta_df <- rbind(meta_df, current_df)
  }
}
dotplot <- meta_df %>%
  group_by(gene) %>% 
  mutate(scaled_expression = (expression - mean(expression)) / sd(expression)) %>% 
  ungroup() %>% 
  mutate(gene = factor(gene, levels = genes)) %>% 
  ggplot(aes(x = time, y = gene, color = scaled_expression, size = fraction_expr)) +
  geom_point() +
  scale_colour_gradientn(colours = c("blue","white","red")) +
  labs(x = "", y = "") +
  theme_classic() +
  theme(axis.text = element_text(size = 13), 
        legend.text = element_text(size = 13), 
        legend.title = element_text(size = 13), 
        legend.position = "bottom", 
        legend.box = "vertical")
dotplot

# saveRDS(dotplot, file = "results/R_objects/ggplots/dotplot_top_genes_signature.rds")

Number of detected genes across time intervals:

pbmc$processing <- case_when(
  pbmc$time %in% c("0h", "2h") ~ "fresh", 
  pbmc$time == "8h" ~ "local",
  pbmc$time %in% c("24h", "48h") ~ "central"
)
df_supp_fig <- dplyr::select(pbmc@meta.data, "processing", "nFeature_RNA")
# saveRDS(df_supp_fig, "results/R_objects/ggplots/dataframe_ngenesVSprocessing_pbmc.rds")
palette <- c("#999999", "#92e8df", "#632c63", "#e4624e", "#c0e212")
n_detect_genes <- pbmc@meta.data %>%
  mutate(is_biased = factor(is_biased, c("unbiased", "biased"))) %>% 
  ggplot(aes(is_biased, nFeature_RNA, fill = is_biased)) +
    geom_boxplot() +
    labs(x = "", y = "Number of Detected Genes") +
    theme_classic() +
    theme(legend.position = "none")
n_detect_genes

t <- t.test(
  nFeature_RNA ~ is_biased, 
  data = pbmc@meta.data, 
  alternative = "two.sided"
)
t$p.value
## [1] 3.909234e-159

Then, we will perform the analysis for each cell type separately, as this will allow us to elucidate the specificity of the signature downstream:

pbmc_types <- SplitObject(pbmc, split.by = "cell_type")
pbmc_types <- purrr::map(pbmc_types, pre_process_seurat)
dea_list <- purrr::map(pbmc_types, function(seurat) {
  seurat$is_biased <- ifelse(seurat$time %in% c("0h", "2h"), "unbiased", "biased")
  Idents(seurat) <- "is_biased"
  dea <- FindMarkers(seurat, ident.1 = "biased", test.use = "wilcox", logfc.threshold = 0, min.pct = 0)
  dea <- dea %>%
    rownames_to_column(var = "gene") %>% 
    mutate(is_significant = ifelse(p_val_adj < 0.001, TRUE, FALSE))
  avg_expr <- rowMeans(as.matrix(seurat[["RNA"]]@data[dea$gene, ]))
  dea$avg_expr <- avg_expr
  dea
})
DT::datatable(dea_list$Monocyte)
DT::datatable(dea_list$T)
DT::datatable(dea_list$NK)
DT::datatable(dea_list$B)
# saveRDS(dea_list, "results/R_objects/dea_results_per_cell_type.rds")
# dea_list <- readRDS("results/R_objects/dea_results_per_cell_type.rds")

Let us assess the overall distribution of the diferentially expressed genes (DEG) with an MA plot:

ma_plot_list <- purrr::map2(dea_list, names(dea_list), function(dea, donor) {
  subset_sig <- filter(dea, is_significant & log(avg_expr + 1) > 0.4 & abs(avg_logFC) > 0.5)
  dea %>% 
  ggplot(aes(log(avg_expr + 1), avg_logFC, color = is_significant)) +
    geom_point() +
    geom_smooth(method = "loess", color = "darkblue") +
    geom_hline(yintercept = 0, color = "black", linetype = "dashed") +
    geom_text_repel(data = subset_sig, aes(label = gene), color = "black") +
    scale_color_manual(values = c("gray78", "green4"), labels = c("sig", "no sig")) +
    labs(title = donor, x = "log (Average Expression)", y = "log (biased / unbiased)", color = "") +
    theme_classic2() +
    theme(axis.title = element_text(size = 11),
          legend.text = element_text(size = 11),
          plot.title = element_text(hjust = 0.5, face = "bold"))

})
ma_plot_list
## $Monocyte

## 
## $T

## 
## $NK

## 
## $B

Of note, we observe a very strong upregulation of FTH1 in all cell types. This gene encodes the heavy subunit of ferritin, whose function is to maintain intracellular iron balance. This function is particularly important in oxidative stress conditions (likely present in our study), as an excess of iron can increase the formation of reactive oxygen species (ROS). Thus, the time-dependent upregulation of FTH1 observed until 24h can serve as a protective mechanism against such stress. Moreover, in most cell types we also observe the upregulation of Cold Inducible RNA Binding Protein (CIRBP) which is the master regulator of the response to cold-shock:

Idents(pbmc) <- "time"
RidgePlot(pbmc, features = c("CIRBP"))

Thus, this is consistent with the fact that we are taking cells out of its physiological niche (~37ºC) and placing them at RT (~20ºC). Furthermore:

pbmc$is_biased <- ifelse(pbmc$time %in% c("0h", "2h"), "unbiased", "biased")
pbmc@meta.data %>% 
  mutate(is_biased = factor(is_biased, levels = c("unbiased", "biased"))) %>% 
  ggplot(aes(is_biased, nFeature_RNA, fill = is_biased)) +
    geom_boxplot() +
    labs(x = "", y = "# Detected Genes") +
    theme_classic() +
    theme(legend.position = "none")

In the biased samples there is an increased dropout rate and a decreased number of detected genes. This can be attributed to a lowered rate of transcription given the cold shock.

Finally, we also speculate that some genes increase their expression due to ex vivo incubation (and independently of the temperature). For instance, the up-regulation of CXCR4 suggests a lack of exposure of its ligand (CXCL12) in the lymph node microenvironment.

4 Cell type specificity

deg_100 <- purrr::map(dea_list, ~.x$gene[1:100])
deg_100 <- deg_100[levels(pbmc$cell_type)]
names(deg_100) <- c("T-cell", "NK", "Monocyte", "B-cell")
all_genes <- Reduce(union, deg_100)
cell_types <- names(deg_100)
matr_meta <- matrix(, nrow = length(all_genes), ncol = length(cell_types))
for (i  in 1:length(all_genes)) {
  new_row <- as.numeric(map_dbl(deg_100, ~ all_genes[i] %in% .))
  matr_meta[i, ] <- new_row
}
rownames(matr_meta) <- all_genes
colnames(matr_meta) <- names(deg_100)
matr_meta <- matr_meta[order(rowSums(matr_meta), decreasing = TRUE), ]
cols <- colorRampPalette(c("gray99", "blue4"))(2)
heatmap_metasignatures <- pheatmap(
  matr_meta, 
  color = cols, 
  cluster_rows = FALSE, 
  cluster_cols = FALSE, 
  fontsize = 5,
  gaps_col = 1:4,
  legend = FALSE,
  show_rownames = FALSE, 
  show_colnames = TRUE,
  fontsize_col = 12,
  angle_col = 45
)
print(heatmap_metasignatures)

# saveRDS(object = heatmap_metasignatures, file = "results/R_objects/ggplots/heatmap_deg_pbmc.rds")
# saveRDS(object = deg_100, file = "results/R_objects/deg_100_pbmc.rds")

Cell-type signatures:

# Score with cell type-specific markers
pbmc0 <- subset(pbmc, subset = time == "0h")
Idents(pbmc0) <- "cell_type"
markers <- FindAllMarkers(pbmc0, test.use = "wilcox")
markers$male[markers$male$cluster == "2", ]
## NULL
t_cell_mark <- c("CD3D", "IL7R", "LTB", "CD3E", "FCER1G", "TYROBP")
nk_mark <- c("GNLY", "NKG7", "GZMB", "FGFBP2", "CST7", "KLRF1", "GZMA", "CTSW", "CCL4", "SPON2", "PSMA1")
monocyte_mark <- c("S100A9", "LYZ", "S100A8", "CST3")
b_mark <- c("IGLL5", "CD79A", "MS4A1", "TCL1A", "CD79B", "HLA-DQA1", "LINC00926", "FCER2", "BANK1", 
            "VPREB3", "CD19", "BLK", "CD22", "IGJ", "TLR10", "BLNK")
markers_list <- list(t_cell = t_cell_mark, nk = nk_mark, monocyte = monocyte_mark, b = b_mark)
pbmc_types <- purrr::map(pbmc_types, function(seurat) {
  seurat <- AddModuleScore(
    seurat, 
    features = markers_list, 
    name = c("t_score", "nk_score", "monocyte_score", "b_score")
  )
  seurat
})

# 
selected_scores <- c("t_score1", "nk_score2", "monocyte_score3", "b_score4")
pbmc_types <- pbmc_types[c("T", "NK", "Monocyte", "B")]
ridge_df <- purrr::map2(pbmc_types, selected_scores, function(seurat, score) {
  df <- data.frame(
    time = factor(seurat$time, levels = rev(levels(seurat$time))),
    is_biased = factor(seurat$is_biased, levels = c("unbiased", "biased")),
    cell_type_score = seurat@meta.data[, score]
  )
  df
})
new_names <- c("T-cell", "NK", "Monocyte", "B-cell")
names(ridge_df) <- new_names
ridge_gg_l <- purrr::map2(ridge_df, names(ridge_df), function(df, title) {
  p <- ggplot(df, aes(cell_type_score, time, fill = is_biased)) +
    geom_density_ridges() +
    scale_fill_manual(values = c("azure3", "firebrick2")) +
    labs(title = title, x = "Cell type score", y = "", fill = "") +
    theme_classic() +
    theme(plot.title = element_text(hjust = 0.5, size = 12))
  p
})
ridge_gg_l$`T-cell` <- ridge_gg_l$`T-cell` +
  scale_x_continuous(breaks = c(-1, 0, 1)) +
  theme(axis.text.y = element_text(size = 11),
        axis.title.x = element_blank(),
        plot.margin = unit(c(0.3,0,0.25,0), units = "cm"))
ridge_gg_l$NK <- ridge_gg_l$NK + 
  theme(axis.line.y = element_blank(), 
        axis.text.y = element_blank(), 
        axis.ticks.y = element_blank(),
        axis.title.x = element_blank(),
        plot.margin = unit(c(0.3,0,0.25,0), units = "cm"))
ridge_gg_l$Monocyte <- ridge_gg_l$Monocyte + 
  theme(axis.line.y = element_blank(), 
        axis.text.y = element_blank(), 
        axis.ticks.y = element_blank(),
        axis.title.x = element_blank(),
        plot.margin = unit(c(0.3,0,0.25,0), units = "cm"))
ridge_gg_l$`B-cell` <- ridge_gg_l$`B-cell` + 
  theme(axis.line.y = element_blank(), 
        axis.text.y = element_blank(), 
        axis.ticks.y = element_blank(),
        axis.title.x = element_blank(),
        plot.margin = unit(c(0.3,0,0.25,0), units = "cm"))
leg <- as_ggplot(get_legend(ridge_gg_l$`B-cell` + theme(legend.position = "bottom")))
# ggsave(
#   filename = "../doc/figures/legends/ridge_plot_legend.pdf", 
#   plot = leg, 
#   width = 9, 
#   height = 5,
#   units = "cm"
# )
ridge_gg_arr <- ggarrange(
  plotlist = ridge_gg_l,
  nrow = 1, ncol = 4,
  legend = "none",
  widths = c(1,0.8,0.8,0.8,0.8)
)
ridge_gg_arr

# saveRDS(ridge_gg_arr, "results/R_objects/ggplots/ridge_plot_scores.rds")

These results suggest that (1) the gene signatures are partially cell type-specific and (2) cells lose their identity in a time-dependent manner.

5 Gene Ontology Enrichment

All cell types:

top_list <- list(
  down = dea_general$gene[dea_general$avg_logFC < 0], 
  up = dea_general$gene[dea_general$avg_logFC > 0], 
  universe = rownames(pbmc)
)
top_entrez <- purrr::map(top_list, function(x) {
  entrez <- AnnotationDbi::select(
    x = org.Hs.eg.db, 
    keys = x, 
    keytype = "SYMBOL",
    columns = "ENTREZID"
  )$ENTREZID
  entrez <- entrez[!is.na(entrez)]
  entrez
})
top_go <- purrr::map(
  top_entrez[c("down", "up")], 
  get_GOenrichment, 
  universe = top_entrez$universe
)
top_go <- purrr::map(top_go, function(go) {
  selection <- go$Size >= 3 & go$Size <= 600 & go$Count >= 5 & go$OddsRatio > 2 & go$Pvalue < 0.05
  go <- go[selection, ]
  go[order(go$OddsRatio, decreasing = TRUE), ]
})
top_go_rbind <- bind_rows(top_go, .id = "direction")
# WriteXLS::WriteXLS(top_go_rbind, "results/tables/go_pbmc_all.xlsx", SheetNames = "PBMC")
top_go <- top_go %>% 
  purrr::map(~ .x[1:2, ]) %>% 
  bind_rows(.id = "direction")
top_go_gg <- top_go %>% 
  mutate(direction = factor(direction, levels = c("up", "down")),
         Term = factor(Term, levels = rev(top_go$Term))) %>% 
  ggplot(aes(Term, -1 * log10(Pvalue), color = direction)) +
    geom_segment(aes(x = Term, xend = Term, y = 0, yend = -1 * log10(Pvalue))) +
    geom_point() +
    scale_color_manual("", values = c("firebrick3", "dodgerblue3")) +
    labs(x = "", y = "-log10 (p-value)", color = "") +
    theme_light() +
    coord_flip()
top_go_gg

# saveRDS(object = top_go_gg, "results/R_objects/ggplots/lollipop_go_enrichment_pbmc.rds")

Cell type-specific:

deg_cell_type <- purrr::map(dea_list, function(df) {
  df_down <- df[df$avg_logFC < 0, ]
  df_up <- df[df$avg_logFC > 0, ]
  out_list <- list(down = df_down$gene[1:200], up = df_up$gene[1:200])
})
deg_cell_type_entrez <- purrr::map(deg_cell_type, function(l) {
  entrez_l <- purrr::map(l, function(x) {
    entrez <- AnnotationDbi::select(
      x = org.Hs.eg.db, 
      keys = x, 
      keytype = "SYMBOL",
      columns = "ENTREZID"
    )$ENTREZID
    entrez <- entrez[!is.na(entrez)]
    entrez
  })
  entrez_l
})
universe_entrez <- AnnotationDbi::select(
  x = org.Hs.eg.db, 
  keys = rownames(pbmc), 
  keytype = "SYMBOL",
  columns = "ENTREZID"
)$ENTREZID
go_cell_type <- purrr::map(deg_cell_type_entrez, function(l) {
  go <- purrr::map(l, function(deg_list) {
    get_GOenrichment(target = deg_list, universe = universe_entrez)
  })
})
go_cell_type_filt <- purrr::map(go_cell_type, function(l) {
  go_filt <- purrr::map(l, function(go) {
    selection <- go$Size >= 3 & go$Size <= 600 & go$Count >= 5 & go$OddsRatio > 2 & go$Pvalue < 0.05
    go <- go[selection, ]
    go[order(go$OddsRatio, decreasing = TRUE), ]
  })
  go_filt
})
go_cell_type_filt
## $Monocyte
## $Monocyte$down
##          GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                                            Term
## 291  GO:0007159 4.564589e-05 16.031056  0.4189803     5   20                                                                    leukocyte cell-cell adhesion
## 292  GO:0034314 4.827940e-05 15.828343  0.4238019     5   20                                                        Arp2/3 complex-mediated actin nucleation
## 355  GO:0006120 2.117203e-07 12.850415  0.9109496     9   43                                            mitochondrial electron transport, NADH to ubiquinone
## 428  GO:0030838 1.893861e-07 10.775733  1.1715095    10   55                                            positive regulation of actin filament polymerization
## 429  GO:0032981 1.893861e-07 10.775733  1.1715095    10   55                                              mitochondrial respiratory chain complex I assembly
## 439  GO:0021762 3.245639e-04  9.827629  0.6177050     5   29                                                                    substantia nigra development
## 506  GO:0042773 5.653366e-08  9.182842  1.6188131    12   76                                                        ATP synthesis coupled electron transport
## 507  GO:0008064 1.803405e-09  8.997255  2.0874169    15   98                                          regulation of actin polymerization or depolymerization
## 519  GO:0035722 1.801642e-04  8.363861  0.8520069     6   40                                                       interleukin-12-mediated signaling pathway
## 520  GO:0038096 5.402030e-06  8.221785  1.3137859     9   62                                    Fc-gamma receptor signaling pathway involved in phagocytosis
## 521  GO:0098869 7.450219e-04  7.987879  0.7338431     5   35                                                                 cellular oxidant detoxification
## 571  GO:0046209 2.714268e-04  7.682797  0.9159074     6   43                                                                  nitric oxide metabolic process
## 572  GO:0070671 2.714268e-04  7.682797  0.9159074     6   43                                                                      response to interleukin-12
## 574  GO:0098754 3.165365e-05  7.508497  1.2567102     8   59                                                                                  detoxification
## 575  GO:0043312 7.358333e-20  7.433697  7.9019584    42  373                                                                        neutrophil degranulation
## 576  GO:0002479 1.227153e-05  7.338776  1.4484117     9   68 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
## 577  GO:0022900 7.437181e-09  7.330100  2.6625215    16  125                                                                        electron transport chain
## 580  GO:0042119 5.433856e-19  7.183026  7.9049556    41  375                                                                           neutrophil activation
## 584  GO:0042742 1.192117e-03  7.103934  0.8112927     5   39                                                                   defense response to bacterium
## 585  GO:0042136 3.955897e-04  7.103892  0.9798079     6   46                                                           neurotransmitter biosynthetic process
## 587  GO:0032411 1.292017e-03  6.969884  0.8260066     5   39                                                     positive regulation of transporter activity
## 588  GO:0002444 1.167789e-17  6.883636  7.7265519    39  369                                                             myeloid leukocyte mediated immunity
## 589  GO:0002252 1.561691e-04  6.849728  1.1724418     7   71                                                                         immune effector process
## 593  GO:0002275 2.212016e-18  6.691929  8.6434290    42  408                                             myeloid cell activation involved in immune response
## 601  GO:0045333 2.603522e-05  6.602366  1.5860870     9   76                                                                            cellular respiration
## 642  GO:0045321 1.727748e-14  6.401825  6.8483419    33  346                                                                            leukocyte activation
## 644  GO:0048013 6.966268e-04  6.310579  1.0863088     6   51                                                               ephrin receptor signaling pathway
## 647  GO:0006887 8.387089e-18  6.287744  9.4348968    43  449                                                                                      exocytosis
## 650  GO:0009308 1.070452e-04  6.197482  1.4844039     8   70                                                                         amine metabolic process
## 657  GO:0046034 1.445854e-06  5.949516  2.5590943    13  121                                                                           ATP metabolic process
## 658  GO:0045454 9.477973e-04  5.913922  1.1502093     6   54                                                                          cell redox homeostasis
## 659  GO:0030595 2.491887e-03  5.911145  0.9545962     5   45                                                                            leukocyte chemotaxis
## 660  GO:0032760 2.495299e-03  5.908683  0.9548483     5   45                                         positive regulation of tumor necrosis factor production
## 708  GO:0019884 3.936281e-07  5.710078  3.0885250    15  145                                        antigen processing and presentation of exogenous antigen
## 709  GO:0048002 4.018884e-07  5.699665  3.0933728    15  146                                          antigen processing and presentation of peptide antigen
## 710  GO:0006521 3.007340e-03  5.635158  0.9956891     5   47                                             regulation of cellular amino acid metabolic process
## 711  GO:0051235 3.494218e-05  5.596951  2.0482707    10   98                                                                         maintenance of location
## 723  GO:0046903 1.272428e-14  5.366313 10.0586033    40  506                                                                                       secretion
## 725  GO:0002576 1.608670e-03  5.283133  1.2710925     6   60                                                                          platelet degranulation
## 728  GO:0002263 2.665107e-15  5.231092 10.9963045    43  519                                                     cell activation involved in immune response
## 733  GO:0032412 4.167429e-03  5.183794  1.0723562     5   51                                            regulation of ion transmembrane transporter activity
## 779  GO:0032956 3.342827e-06  5.062613  3.1926164    14  153                                                   regulation of actin cytoskeleton organization
## 784  GO:1903555 2.097763e-04  4.902231  2.0661167     9   97                             regulation of tumor necrosis factor superfamily cytokine production
## 785  GO:0007229 5.199431e-03  4.898934  1.1289091     5   53                                                             integrin-mediated signaling pathway
## 795  GO:0006909 1.231139e-03  4.725485  1.6442092     7   81                                                                                    phagocytosis
## 802  GO:0007005 1.630310e-05  4.661281  3.1821637    13  157                                                                      mitochondrion organization
## 810  GO:0010950 1.492565e-04  4.627773  2.4282197    10  114                                                   positive regulation of endopeptidase activity
## 845  GO:0060337 7.482698e-03  4.455429  1.2297830     5   58                                                             type I interferon signaling pathway
## 846  GO:0002504 3.541224e-03  4.451995  1.4829412     6   70       antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
## 847  GO:2000116 8.387677e-04  4.436932  1.9997520     8   96                                              regulation of cysteine-type endopeptidase activity
## 856  GO:0019886 3.904414e-03  4.357807  1.5123122     6   71               antigen processing and presentation of exogenous peptide antigen via MHC class II
## 857  GO:0034340 3.904414e-03  4.357807  1.5123122     6   71                                                                   response to type I interferon
## 859  GO:0006919 8.191178e-03  4.351301  1.2567102     5   59                activation of cysteine-type endopeptidase activity involved in apoptotic process
## 903  GO:0032091 9.408953e-03  4.194834  1.2993105     5   61                                                          negative regulation of protein binding
## 904  GO:0032535 1.255250e-05  4.194645  4.0669951    15  192                                                           regulation of cellular component size
## 905  GO:0051179 9.965242e-03  4.168432  1.3240475     5  101                                                                                    localization
## 907  GO:0055086 1.377714e-06  4.125007  5.3378241    19  253                                          nucleobase-containing small molecule metabolic process
## 908  GO:0009144 4.467631e-06  4.124412  4.7218935    17  224                                                purine nucleoside triphosphate metabolic process
## 910  GO:1902903 7.181027e-04  4.081469  2.4370113     9  119                                                 regulation of supramolecular fiber organization
## 912  GO:0031333 5.315472e-03  4.068330  1.6096540     6   76                                                 negative regulation of protein complex assembly
## 919  GO:0009126 6.929305e-06  3.977050  4.8777395    17  229                                               purine nucleoside monophosphate metabolic process
## 923  GO:0009199 8.244343e-06  3.920036  4.9416400    17  232                                                   ribonucleoside triphosphate metabolic process
## 935  GO:0010959 3.602610e-03  3.851703  1.9826303     7   94                                                               regulation of metal ion transport
## 949  GO:0097237 1.101792e-03  3.823986  2.5871039     9  122                                                            cellular response to toxic substance
## 951  GO:0045087 1.131734e-03  3.810534  2.5980265     9  138                                                                          innate immune response
## 953  GO:0034764 7.434926e-03  3.771976  1.7253140     6   81                                                  positive regulation of transmembrane transport
## 954  GO:0009161 1.363719e-05  3.758156  5.1333415    17  241                                                  ribonucleoside monophosphate metabolic process
## 963  GO:0009314 8.043243e-03  3.705628  1.7541829     6   83                                                                           response to radiation
## 966  GO:0031145 1.552432e-02  3.666760  1.4697119     5   69                                          anaphase-promoting complex-dependent catabolic process
## 967  GO:0060071 1.552432e-02  3.666760  1.4697119     5   69                                             Wnt signaling pathway, planar cell polarity pathway
## 968  GO:0051092 2.611351e-03  3.657343  2.3856193     8  112                                  positive regulation of NF-kappaB transcription factor activity
## 969  GO:0071222 1.569025e-02  3.655478  1.4735017     5   70                                                         cellular response to lipopolysaccharide
## 970  GO:0050729 1.573462e-02  3.652456  1.4745011     5   70                                                    positive regulation of inflammatory response
## 971  GO:0002793 5.034472e-03  3.606061  2.1063830     7   99                                                        positive regulation of peptide secretion
## 994  GO:0098660 1.034114e-05  3.536029  6.1131495    19  287                                                           inorganic ion transmembrane transport
## 995  GO:0043900 1.774950e-02  3.533297  1.5199093     5   74                                                            regulation of multi-organism process
## 997  GO:0002253 4.018213e-04  3.497592  3.7953424    12  191                                                                   activation of immune response
## 999  GO:0080134 3.555800e-07  3.472213  9.2175049    27  441                                                                regulation of response to stress
## 1007 GO:0008360 1.158893e-02  3.404949  1.8957153     6   89                                                                        regulation of cell shape
## 1008 GO:0016310 8.689210e-04  3.398428  3.5799714    11  184                                                                                 phosphorylation
## 1011 GO:0001736 2.154829e-02  3.349915  1.5975129     5   75                                                                establishment of planar polarity
## 1049 GO:0033209 2.334866e-02  3.274724  1.6308301     5   78                                                tumor necrosis factor-mediated signaling pathway
## 1050 GO:0002695 1.385619e-02  3.264645  1.9706788     6   93                                                     negative regulation of leukocyte activation
## 1051 GO:0060759 2.375957e-02  3.259731  1.6385006     5   77                                                     regulation of response to cytokine stimulus
## 1056 GO:0045861 3.348514e-03  3.208230  3.0392496     9  144                                                              negative regulation of proteolysis
## 1057 GO:0071216 5.477112e-03  3.205985  2.6928008     8  127                                                            cellular response to biotic stimulus
## 1058 GO:0098609 1.497295e-02  3.205330  2.0045738     6   98                                                                              cell-cell adhesion
## 1059 GO:0010639 5.507338e-03  3.203313  2.6955763     8  128                                                   negative regulation of organelle organization
## 1061 GO:0045088 3.665984e-04  3.166529  4.8828717    14  234                                                            regulation of innate immune response
## 1070 GO:0008637 2.840499e-02  3.098802  1.7170323     5   81                                                                 apoptotic mitochondrial changes
## 1076 GO:0071241 1.757975e-02  3.084468  2.0771411     6   98                                                        cellular response to inorganic substance
## 1087 GO:0002764 1.824185e-02  3.056970  2.0943613     6  105                                                    immune response-regulating signaling pathway
## 1090 GO:0051224 1.880258e-02  3.034962  2.1087171     6   99                                                        negative regulation of protein transport
## 1091 GO:0010638 3.605148e-04  3.034532  5.4666500    15  268                                                   positive regulation of organelle organization
## 1092 GO:0034097 1.675187e-04  3.031842  6.2878945    17  333                                                                            response to cytokine
## 1094 GO:0009259 7.145530e-05  3.031737  7.0277743    19  331                                                                ribonucleotide metabolic process
## 1095 GO:0070838 1.285248e-03  3.027414  4.3239350    12  203                                                                    divalent metal ion transport
## 1096 GO:0002758 1.340708e-03  3.011258  4.3452352    12  204                                           innate immune response-activating signal transduction
## 1097 GO:0006163 1.731467e-04  3.009462  6.2848643    17  300                                                             purine nucleotide metabolic process
## 1099 GO:0043207 4.290095e-06  2.990059 10.4370845    27  490                                                            response to external biotic stimulus
## 1103 GO:0002223 3.314077e-02  2.964888  1.7892145     5   84                                            stimulatory C-type lectin receptor signaling pathway
## 1104 GO:0070374 3.314077e-02  2.964888  1.7892145     5   84                                                    positive regulation of ERK1 and ERK2 cascade
## 1108 GO:0098657 3.134935e-05  2.957255  8.4224063    22  396                                                                                import into cell
## 1111 GO:0038095 2.145763e-02  2.938997  2.1726176     6  102                                                           Fc-epsilon receptor signaling pathway
## 1113 GO:0090263 3.462784e-02  2.927455  1.8105147     5   85                                          positive regulation of canonical Wnt signaling pathway
## 1145 GO:0055082 9.853231e-05  2.863762  7.8171633    20  367                                                                   cellular chemical homeostasis
## 1146 GO:0045862 1.378459e-03  2.854460  4.9629402    13  233                                                              positive regulation of proteolysis
## 1149 GO:0051090 7.140898e-03  2.829779  3.4141414     9  162                                         regulation of DNA-binding transcription factor activity
## 1157 GO:1903532 5.635621e-03  2.757545  3.8979315    10  183                                                        positive regulation of secretion by cell
## 1159 GO:0051607 2.799423e-02  2.751986  2.3099517     6  109                                                                       defense response to virus
## 1164 GO:0051222 1.911779e-02  2.734618  2.7210434     7  129                                                        positive regulation of protein transport
## 1168 GO:1905330 4.441418e-02  2.721138  1.9383157     5   91                                                    regulation of morphogenesis of an epithelium
## 1193 GO:0043123 2.030919e-02  2.698251  2.7543730     7  130                                      positive regulation of I-kappaB kinase/NF-kappaB signaling
## 1194 GO:0098655 9.699322e-03  2.684874  3.5851463     9  177                                                                  cation transmembrane transport
## 1198 GO:0032879 3.552854e-03  2.667857  4.9033347    12  264                                                                      regulation of localization
## 1199 GO:0033002 4.800924e-02  2.658617  1.9809160     5   93                                                                       muscle cell proliferation
## 1201 GO:0044089 5.030226e-03  2.654528  4.4592243    11  211                                            positive regulation of cellular component biogenesis
## 1213 GO:0031349 4.031702e-03  2.609037  4.9627144    12  242                                                         positive regulation of defense response
## 1243 GO:0010942 7.061692e-04  2.557989  7.7447839    18  369                                                               positive regulation of cell death
## 1255 GO:0050708 8.261426e-03  2.466122  4.7712386    11  224                                                                 regulation of protein secretion
## 1257 GO:0051046 1.396636e-03  2.461462  7.5402610    17  354                                                                         regulation of secretion
## 1259 GO:0090087 8.076983e-04  2.457468  8.4987688    19  399                                                                 regulation of peptide transport
## 1263 GO:0070201 3.150466e-02  2.447226  3.0192528     7  148                                             regulation of establishment of protein localization
## 1270 GO:0060341 2.302138e-02  2.439048  3.4747397     8  170                                                             regulation of cellular localization
## 1293 GO:0051346 1.288988e-02  2.414126  4.4091357    10  207                                                       negative regulation of hydrolase activity
## 1295 GO:0043488 3.394986e-02  2.404538  3.0672248     7  144                                                                    regulation of mRNA stability
## 1297 GO:0009617 1.808260e-02  2.402354  3.9751151     9  196                                                                           response to bacterium
## 1300 GO:0050821 4.882589e-02  2.384350  2.6412214     6  124                                                                           protein stabilization
## 1306 GO:0065008 6.729104e-03  2.367629  6.0199637    13  372                                                                regulation of biological quality
## 1307 GO:0061024 2.697872e-02  2.361309  3.5813775     8  179                                                                           membrane organization
## 1312 GO:0051098 1.159606e-02  2.341683  5.0055405    11  235                                                                           regulation of binding
## 1315 GO:0022610 3.412907e-04  2.326874 11.9919970    25  563                                                                             biological adhesion
## 1322 GO:0055085 3.453336e-03  2.306595  7.5342413    16  377                                                                         transmembrane transport
## 1346 GO:0060627 3.233094e-02  2.272781  3.7081930     8  177                                                        regulation of vesicle-mediated transport
## 1355 GO:0043086 2.698324e-02  2.229634  4.2629185     9  207                                                       negative regulation of catalytic activity
## 1358 GO:0032268 2.208602e-02  2.213115  4.8160371    10  254                                                regulation of cellular protein metabolic process
## 1366 GO:0009611 2.909536e-02  2.196902  4.3198607     9  208                                                                            response to wounding
## 1367 GO:0002521 4.995060e-02  2.196135  3.3404202     7  159                                                                       leukocyte differentiation
## 1380 GO:0000165 3.888420e-02  2.186439  3.8475399     8  187                                                                                    MAPK cascade
## 1424 GO:0032870 4.172505e-02  2.046631  4.6157320     9  219                                                           cellular response to hormone stimulus
## 
## $Monocyte$up
##          GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                    Term
## 299  GO:0061844 1.669890e-05 20.967230  0.3486826     5   16 antimicrobial humoral immune response mediated by antimicrobial peptide
## 491  GO:0009409 3.038636e-04 10.012639  0.6101945     5   28                                                        response to cold
## 492  GO:0061045 3.038636e-04 10.012639  0.6101945     5   28                                    negative regulation of wound healing
## 642  GO:1990868 3.070875e-04  7.499289  0.9370845     6   43                                                   response to chemokine
## 646  GO:0071222 1.710086e-05  7.011326  1.5081724     9   70                                 cellular response to lipopolysaccharide
## 661  GO:0006959 1.659172e-04  6.830729  1.1894464     7   55                                                 humoral immune response
## 662  GO:0002576 6.048645e-05  6.790748  1.3729377     8   63                                                  platelet degranulation
## 720  GO:0046545 1.843451e-03  6.386466  0.8934991     5   41                    development of primary female sexual characteristics
## 724  GO:0071456 3.072604e-04  6.110553  1.3106061     7   61                                            cellular response to hypoxia
## 730  GO:1903034 1.582321e-04  5.829142  1.5690717     8   72                                      regulation of response to wounding
## 795  GO:0048661 3.089279e-03  5.604084  1.0024624     5   46                 positive regulation of smooth muscle cell proliferation
## 809  GO:0033002 7.048687e-04  5.251002  1.4996295     7   69                                               muscle cell proliferation
## 811  GO:0030278 3.600356e-04  5.104645  1.7652056     8   81                                              regulation of ossification
## 812  GO:0019935 4.452788e-03  5.103359  1.0896331     5   50                                    cyclic-nucleotide-mediated signaling
## 875  GO:0045766 1.144730e-03  4.797424  1.6256158     7   75                                     positive regulation of angiogenesis
## 888  GO:0071216 3.131718e-05  4.690724  2.9047912    12  134                                    cellular response to biotic stimulus
## 889  GO:0050900 2.814765e-03  4.680847  1.4168445     6   68                                                     leukocyte migration
## 897  GO:0010594 1.489024e-03  4.566529  1.6998276     7   78                                regulation of endothelial cell migration
## 940  GO:0006757 1.855734e-03  4.379730  1.7652056     7   81                                                 ATP generation from ADP
## 941  GO:0042866 1.855734e-03  4.379730  1.7652056     7   81                                           pyruvate biosynthetic process
## 943  GO:0072525 9.456256e-04  4.351606  2.0371875     8   94                       pyridine-containing compound biosynthetic process
## 947  GO:0009166 9.996479e-04  4.311377  2.0544983     8   95                                            nucleotide catabolic process
## 948  GO:0046939 1.050937e-03  4.275590  2.0703029     8   95                                              nucleotide phosphorylation
## 950  GO:0009179 1.125555e-03  4.226466  2.0920955     8   96                     purine ribonucleoside diphosphate metabolic process
## 952  GO:0042107 9.476212e-03  4.189261  1.3019356     5   60                                              cytokine metabolic process
## 995  GO:0070482 3.259791e-06  4.031649  5.1212755    18  235                                               response to oxygen levels
## 997  GO:0014070 3.018270e-03  3.989070  1.9218569     7   92                                     response to organic cyclic compound
## 1006 GO:0097529 3.505360e-03  3.873767  1.9733859     7   91                                             myeloid leukocyte migration
## 1010 GO:0009617 6.250199e-05  3.806653  4.1286870    14  194                                                   response to bacterium
## 1039 GO:0072599 2.396349e-03  3.713609  2.3536075     8  108          establishment of protein localization to endoplasmic reticulum
## 1044 GO:0034404 1.420596e-03  3.677318  2.6823239     9  124               nucleobase-containing small molecule biosynthetic process
## 1045 GO:0009132 2.539100e-03  3.676372  2.3754001     8  109                                nucleoside diphosphate metabolic process
## 1051 GO:0019362 1.583023e-03  3.615610  2.7240827     9  125                                   pyridine nucleotide metabolic process
## 1052 GO:0006754 5.128679e-03  3.593791  2.1138882     7   97                                                ATP biosynthetic process
## 1053 GO:0046434 5.502637e-04  3.589818  3.3778626    11  155                                       organophosphate catabolic process
## 1061 GO:0008285 7.151366e-05  3.561952  4.7196110    15  224                               negative regulation of cell proliferation
## 1062 GO:0007423 1.740010e-02  3.554673  1.5127087     5   71                                               sensory organ development
## 1064 GO:0010634 1.764158e-02  3.542060  1.5181762     5   70                        positive regulation of epithelial cell migration
## 1065 GO:0001568 4.669190e-05  3.532121  5.0890979    16  235                                                blood vessel development
## 1084 GO:0007568 4.229776e-04  3.472170  3.8137158    12  175                                                                   aging
## 1111 GO:0150063 4.145092e-03  3.371705  2.5715341     8  118                                               visual system development
## 1117 GO:0051897 2.233073e-02  3.318166  1.6126570     5   74                       positive regulation of protein kinase B signaling
## 1120 GO:0072358 2.441932e-05  3.304160  6.4942132    19  298                                       cardiovascular system development
## 1121 GO:0001659 1.321439e-02  3.302521  1.9507389     6   90                                                 temperature homeostasis
## 1124 GO:2000116 1.830475e-03  3.267032  3.3342773    10  153                      regulation of cysteine-type endopeptidase activity
## 1127 GO:0009145 8.269014e-03  3.263339  2.3100222     7  106                     purine nucleoside triphosphate biosynthetic process
## 1148 GO:0090130 3.600993e-03  3.170860  3.0727653     9  141                                                        tissue migration
## 1149 GO:0006614 1.572474e-02  3.169187  2.0267176     6   93             SRP-dependent cotranslational protein targeting to membrane
## 1152 GO:0001666 2.631348e-02  3.166476  1.6826430     5   81                                                     response to hypoxia
## 1153 GO:0010951 1.610715e-02  3.150802  2.0374384     6   94                           negative regulation of endopeptidase activity
## 1158 GO:0009201 1.004606e-02  3.135009  2.3971928     7  110                        ribonucleoside triphosphate biosynthetic process
## 1184 GO:0040011 3.242637e-03  3.007716  3.6101155    10  185                                                              locomotion
## 1211 GO:0030334 8.198351e-03  2.978577  2.8847721     8  139                                            regulation of cell migration
## 1214 GO:1903707 3.296757e-02  2.970402  1.7869983     5   82                                      negative regulation of hemopoiesis
## 1219 GO:0000184 1.321305e-02  2.960173  2.5279488     7  116     nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
## 1220 GO:0009127 1.321305e-02  2.960173  2.5279488     7  116                    purine nucleoside monophosphate biosynthetic process
## 1223 GO:1990845 3.448502e-02  2.931947  1.8087909     5   83                                                  adaptive thermogenesis
## 1224 GO:0007548 2.173407e-02  2.930571  2.1792662     6  100                                                     sex differentiation
## 1231 GO:0009156 1.469929e-02  2.893861  2.5815358     7  119                       ribonucleoside monophosphate biosynthetic process
## 1235 GO:0052547 2.001816e-03  2.860310  4.5550900    12  210                                        regulation of peptidase activity
## 1273 GO:0008406 4.098426e-02  2.787507  1.8959616     5   87                                                       gonad development
## 1274 GO:0009607 5.786263e-04  2.782592  6.3388889    16  308                                             response to biotic stimulus
## 1278 GO:0009605 3.248673e-04  2.765683  7.2909066    18  380                                           response to external stimulus
## 1279 GO:1901136 4.224515e-02  2.762629  1.9118627     5   88                               carbohydrate derivative catabolic process
## 1284 GO:0034101 4.271742e-02  2.753572  1.9177542     5   88                                                 erythrocyte homeostasis
## 1285 GO:0070498 4.271742e-02  2.753572  1.9177542     5   88                                interleukin-1-mediated signaling pathway
## 1289 GO:0035239 4.053491e-03  2.738875  4.3333333    11  205                                                      tube morphogenesis
## 1294 GO:0006874 9.681732e-03  2.684938  3.5834156     9  165                                        cellular calcium ion homeostasis
## 1296 GO:0006413 3.111959e-02  2.680301  2.3683884     6  109                                                translational initiation
## 1330 GO:0044057 7.646766e-03  2.627964  4.0752278    10  187                                            regulation of system process
## 1331 GO:0009719 3.406146e-02  2.621622  2.4207981     6  117                                         response to endogenous stimulus
## 1332 GO:0051347 8.402628e-04  2.588852  7.1983195    17  331                             positive regulation of transferase activity
## 1339 GO:0070663 2.598953e-02  2.555229  2.8984240     7  133                                   regulation of leukocyte proliferation
## 1341 GO:0010950 3.802713e-02  2.546134  2.4843635     6  114                           positive regulation of endopeptidase activity
## 1343 GO:0008284 2.577326e-03  2.542912  5.9744617    14  291                               positive regulation of cell proliferation
## 1345 GO:0043123 2.693633e-02  2.534785  2.9202167     7  134              positive regulation of I-kappaB kinase/NF-kappaB signaling
## 1346 GO:0042330 3.727544e-03  2.523156  5.5571288    13  255                                                                   taxis
## 1369 GO:0060759 4.085424e-02  2.499203  2.5279488     6  116                             regulation of response to cytokine stimulus
## 1371 GO:0046394 5.742256e-03  2.483990  5.1866535    12  238                                    carboxylic acid biosynthetic process
## 1373 GO:0001655 4.231645e-02  2.476371  2.5497414     6  117                                           urogenital system development
## 1374 GO:0002793 2.991734e-02  2.475339  2.9855947     7  137                                positive regulation of peptide secretion
## 1376 GO:0006954 2.171167e-02  2.467259  3.4359136     8  169                                                   inflammatory response
## 1381 GO:0006479 4.381130e-02  2.453947  2.5715341     6  118                                                     protein methylation
## 1382 GO:0009108 1.620266e-02  2.450105  3.9008865     9  179                                           coenzyme biosynthetic process
## 1425 GO:0072507 1.540644e-02  2.342890  4.5328737    10  208                                   divalent inorganic cation homeostasis
## 1427 GO:1901137 1.188845e-02  2.333897  5.0252653    11  234                            carbohydrate derivative biosynthetic process
## 1428 GO:0051094 9.088891e-03  2.332031  5.5122766    12  268                            positive regulation of developmental process
## 1429 GO:0010942 2.381001e-03  2.330256  7.9280924    17  369                                       positive regulation of cell death
## 1430 GO:0009260 2.885093e-02  2.327044  3.6264035     8  167                                     ribonucleotide biosynthetic process
## 1433 GO:0000122 7.328407e-04  2.314878 10.4822704    22  481               negative regulation of transcription by RNA polymerase II
## 1453 GO:0006402 4.478501e-02  2.254402  3.2596407     7  150                                                  mRNA catabolic process
## 1470 GO:0042060 4.506747e-02  2.250531  3.2638128     7  158                                                           wound healing
## 1472 GO:0051222 1.525256e-02  2.242840  5.2084462    11  239                                positive regulation of protein transport
## 1473 GO:0045937 1.379138e-03  2.237917 10.2911345    21  477                      positive regulation of phosphate metabolic process
## 1474 GO:1901698 4.743609e-04  2.232056 12.9666338    26  595                                           response to nitrogen compound
## 1475 GO:0055082 9.521171e-03  2.229746  6.2305110    13  288                                           cellular chemical homeostasis
## 1481 GO:0045785 2.379268e-02  2.173742  4.8599606    10  224                                    positive regulation of cell adhesion
## 1485 GO:0034655 2.407973e-03  2.169441 10.0467359    20  467                        nucleobase-containing compound catabolic process
## 1488 GO:0045944 8.909530e-04  2.162663 12.7956989    25  595               positive regulation of transcription by RNA polymerase II
## 1491 GO:0002694 1.227915e-02  2.151965  6.4355775    13  296                                      regulation of leukocyte activation
## 1493 GO:0034248 1.237976e-02  2.149739  6.4428536    13  300                          regulation of cellular amide metabolic process
## 1511 GO:0061458 4.292824e-02  2.138728  3.9236359     8  181                                         reproductive system development
## 1516 GO:0035556 1.404675e-02  2.123808  6.5748876    13  331                                       intracellular signal transduction
## 1520 GO:0032101 9.141428e-03  2.109210  7.6128554    15  356                             regulation of response to external stimulus
## 1521 GO:0044703 1.779835e-02  2.108611  6.0380929    12  282                                     multi-organism reproductive process
## 1532 GO:0043900 2.443010e-02  2.077463  5.5921182    11  258                                    regulation of multi-organism process
## 1535 GO:0032270 2.709855e-03  2.072438 11.6301616    22  553               positive regulation of cellular protein metabolic process
## 
## 
## $T
## $T$down
##          GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                                                                                             Term
## 110  GO:0034314 7.982351e-06 25.597545  0.3055110     5   14                                                                                                         Arp2/3 complex-mediated actin nucleation
## 166  GO:0001916 1.763484e-05 20.721003  0.3526225     5   16                                                                                              positive regulation of T cell mediated cytotoxicity
## 236  GO:0034113 1.171800e-04 12.715157  0.5044978     5   23                                                                                                                   heterotypic cell-cell adhesion
## 292  GO:0002252 1.255925e-08 10.707899  1.4224628    12   73                                                                                                                          immune effector process
## 293  GO:0038093 3.024638e-07 10.181438  1.2295511    10   57                                                                                                                    Fc receptor signaling pathway
## 307  GO:0002479 2.255943e-07  9.058688  1.4986457    11   68                                                  antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
## 347  GO:0008064 2.898117e-09  8.661475  2.1598129    15   98                                                                                           regulation of actin polymerization or depolymerization
## 356  GO:0035722 2.169621e-04  8.067664  0.8815563     6   40                                                                                                        interleukin-12-mediated signaling pathway
## 360  GO:0038096 7.149149e-06  7.923858  1.3596156     9   62                                                                                     Fc-gamma receptor signaling pathway involved in phagocytosis
## 363  GO:0070527 9.333728e-04  7.579502  0.7713617     5   35                                                                                                                             platelet aggregation
## 414  GO:0070671 3.262490e-04  7.410717  0.9476730     6   43                                                                                                                       response to interleukin-12
## 415  GO:0048013 1.146508e-04  7.306158  1.1239842     7   51                                                                                                                ephrin receptor signaling pathway
## 416  GO:0002478 1.279356e-05  7.305256  1.4568837     9   67                                                                                 antigen processing and presentation of exogenous peptide antigen
## 419  GO:0098609 5.555934e-05  6.869506  1.3555300     8   66                                                                                                                               cell-cell adhesion
## 421  GO:0002709 5.342335e-04  6.684337  1.0358286     6   47                                                                                                           regulation of T cell mediated immunity
## 464  GO:0060337 1.917364e-03  6.327071  0.9015442     5   41                                                                                                              type I interferon signaling pathway
## 465  GO:0031343 1.936865e-03  6.311462  0.9035952     5   41                                                                                                              positive regulation of cell killing
## 466  GO:0032677 1.936865e-03  6.311462  0.9035952     5   41                                                                                                           regulation of interleukin-8 production
## 468  GO:0006521 7.486214e-04  6.226222  1.1019453     6   50                                                                                              regulation of cellular amino acid metabolic process
## 469  GO:0006955 1.106317e-04  6.154548  1.4898517     8   90                                                                                                                                  immune response
## 471  GO:0032271 4.557132e-07  6.098193  2.7107855    14  123                                                                                                             regulation of protein polymerization
## 472  GO:0002824 2.374735e-03  5.994068  0.9452884     5   43 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
## 473  GO:0006909 8.406160e-06  5.978645  2.1369114    11  100                                                                                                                                     phagocytosis
## 476  GO:0032956 3.456776e-06  5.968558  2.3466600    12  108                                                                                                    regulation of actin cytoskeleton organization
## 482  GO:0038061 1.049989e-03  5.792899  1.1731844     6   54                                                                                                                          NIK/NF-kappaB signaling
## 483  GO:0071346 2.768479e-03  5.762500  0.9780179     5   45                                                                                                            cellular response to interferon-gamma
## 484  GO:0045454 1.131431e-03  5.704480  1.1901010     6   54                                                                                                                           cell redox homeostasis
## 487  GO:0002474 1.972866e-04  5.624810  1.6185720     8   75                                                                           antigen processing and presentation of peptide antigen via MHC class I
## 517  GO:0033209 2.651865e-04  5.363901  1.6887294     8   78                                                                                                 tumor necrosis factor-mediated signaling pathway
## 518  GO:0001906 3.873261e-03  5.287117  1.0550674     5   49                                                                                                                                     cell killing
## 525  GO:0031145 7.658134e-04  5.173200  1.5206846     7   69                                                                                           anaphase-promoting complex-dependent catabolic process
## 526  GO:0009308 8.145698e-04  5.113710  1.5361854     7   70                                                                                                                          amine metabolic process
## 561  GO:0019882 4.460448e-04  4.928096  1.8211261     8   85                                                                                                              antigen processing and presentation
## 568  GO:0032535 9.153550e-07  4.686389  4.2088670    17  192                                                                                                            regulation of cellular component size
## 572  GO:0071897 6.954720e-03  4.547674  1.2094670     5   55                                                                                                                         DNA biosynthetic process
## 574  GO:0002253 2.887394e-06  4.515854  4.0854322    16  191                                                                                                                    activation of immune response
## 576  GO:0060402 3.454560e-03  4.481380  1.4766067     6   67                                                                                                               calcium ion transport into cytosol
## 585  GO:0010950 1.974258e-04  4.460059  2.5124354    10  114                                                                                                    positive regulation of endopeptidase activity
## 607  GO:0050852 1.139607e-04  4.379110  2.8213271    11  129                                                                                                                T cell receptor signaling pathway
## 610  GO:0010972 4.002489e-03  4.338013  1.5206846     6   69                                                                                     negative regulation of G2/M transition of mitotic cell cycle
## 611  GO:0060071 4.002489e-03  4.338013  1.5206846     6   69                                                                                              Wnt signaling pathway, planar cell polarity pathway
## 612  GO:0050900 8.459762e-03  4.314557  1.2664908     5   60                                                                                                                              leukocyte migration
## 617  GO:0031334 1.439035e-04  4.254645  2.8955962    11  133                                                                                                  positive regulation of protein complex assembly
## 618  GO:0002429 1.574128e-07  4.224703  6.1047771    22  277                                                                               immune response-activating cell surface receptor signaling pathway
## 621  GO:0034340 4.612298e-03  4.203468  1.5647624     6   71                                                                                                                    response to type I interferon
## 624  GO:0002223 2.438965e-03  4.157505  1.8512682     7   84                                                                                             stimulatory C-type lectin receptor signaling pathway
## 631  GO:0031146 5.287992e-03  4.076956  1.6088402     6   73                                                                          SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
## 658  GO:1902036 1.080495e-02  4.047106  1.3443733     5   61                                                                                            regulation of hematopoietic stem cell differentiation
## 663  GO:0001736 6.033583e-03  3.957778  1.6529180     6   75                                                                                                                 establishment of planar polarity
## 665  GO:1902903 9.664640e-04  3.902677  2.5403997     9  119                                                                                                  regulation of supramolecular fiber organization
## 666  GO:0042773 6.433842e-03  3.900743  1.6749569     6   76                                                                                                         ATP synthesis coupled electron transport
## 671  GO:0045862 3.059441e-04  3.871679  3.1549857    11  144                                                                                                               positive regulation of proteolysis
## 672  GO:0048584 6.169618e-06  3.867143  5.3934128    18  271                                                                                                      positive regulation of response to stimulus
## 675  GO:0046034 3.761076e-03  3.821768  1.9987514     7   92                                                                                                                            ATP metabolic process
## 676  GO:0070588 2.104939e-03  3.798666  2.3059840     8  105                                                                                                              calcium ion transmembrane transport
## 677  GO:0002703 6.436540e-04  3.793287  2.9091357    10  132                                                                                                        regulation of leukocyte mediated immunity
## 690  GO:0051260 2.352707e-03  3.725988  2.3469514     8  108                                                                                                                      protein homooligomerization
## 707  GO:0009199 1.354363e-03  3.705939  2.6647529     9  122                                                                                                    ribonucleoside triphosphate metabolic process
## 712  GO:0061418 1.579071e-02  3.652670  1.4766067     5   67                                                               regulation of transcription from RNA polymerase II promoter in response to hypoxia
## 716  GO:0034612 1.817623e-04  3.602410  4.0110810    13  182                                                                                                                response to tumor necrosis factor
## 723  GO:0022900 1.711083e-03  3.572160  2.7548633     9  125                                                                                                                         electron transport chain
## 726  GO:1903555 5.450008e-03  3.551098  2.1377739     7   97                                                                              regulation of tumor necrosis factor superfamily cytokine production
## 729  GO:0009144 1.887128e-03  3.518174  2.7944112     9  128                                                                                                 purine nucleoside triphosphate metabolic process
## 734  GO:0002684 1.490400e-05  3.449700  6.2898364    19  313                                                                                                     positive regulation of immune system process
## 754  GO:0070498 1.285697e-02  3.324827  1.9394238     6   88                                                                                                         interleukin-1-mediated signaling pathway
## 756  GO:0050776 7.800158e-03  3.303153  2.2850744     7  118                                                                                                                    regulation of immune response
## 762  GO:0044409 2.454444e-02  3.231938  1.6529180     5   75                                                                                                                                  entry into host
## 763  GO:0051806 2.454444e-02  3.231938  1.6529180     5   75                                                                              entry into cell of other organism involved in symbiotic interaction
## 764  GO:2000116 1.989528e-03  3.227542  3.3719527    10  153                                                                                               regulation of cysteine-type endopeptidase activity
## 765  GO:0052547 3.124754e-04  3.218835  4.8044817    14  218                                                                                                                 regulation of peptidase activity
## 766  GO:0043312 6.186688e-06  3.218304  8.1776081    23  373                                                                                                                         neutrophil degranulation
## 768  GO:0055074 8.076990e-04  3.208342  4.0992366    12  186                                                                                                                          calcium ion homeostasis
## 770  GO:1905330 1.498702e-02  3.206256  2.0055405     6   91                                                                                                     regulation of morphogenesis of an epithelium
## 772  GO:1903706 9.110559e-03  3.199415  2.3530599     7  111                                                                                                                        regulation of hemopoiesis
## 774  GO:0042119 6.856282e-06  3.196224  8.2285503    23  375                                                                                                                            neutrophil activation
## 791  GO:0060759 2.705328e-02  3.144268  1.6956576     5   77                                                                                                      regulation of response to cytokine stimulus
## 792  GO:0043900 6.123010e-03  3.143149  2.7446169     8  126                                                                                                             regulation of multi-organism process
## 795  GO:2000027 1.064701e-02  3.097765  2.4242797     7  110                                                                                                         regulation of animal organ morphogenesis
## 796  GO:0042180 4.257376e-03  3.085206  3.1515637     9  143                                                                                                                cellular ketone metabolic process
## 799  GO:1903039 4.337708e-03  3.075740  3.1605425     9  144                                                                                              positive regulation of leukocyte cell-cell adhesion
## 801  GO:0002244 1.115844e-02  3.067587  2.4463186     7  111                                                                                                    hematopoietic progenitor cell differentiation
## 802  GO:0002764 8.620124e-06  3.064753  8.9477961    24  406                                                                                                     immune response-regulating signaling pathway
## 803  GO:0002444 1.980996e-05  3.054634  8.1713507    22  375                                                                                                              myeloid leukocyte mediated immunity
## 804  GO:0002275 2.026063e-05  3.049637  8.1830098    22  376                                                                                              myeloid cell activation involved in immune response
## 809  GO:0006875 4.140058e-04  2.986901  5.5317656    15  251                                                                                                                   cellular metal ion homeostasis
## 811  GO:0051235 2.238759e-03  2.975912  4.0110810    11  182                                                                                                                          maintenance of location
## 827  GO:0072503 2.279572e-03  2.968667  4.0204888    11  183                                                                                                   cellular divalent inorganic cation homeostasis
## 828  GO:0009259 3.768489e-03  2.935320  3.6825397    10  168                                                                                                                 ribonucleotide metabolic process
## 830  GO:0002263 3.216358e-06  2.915263 11.5263482    29  523                                                                                                      cell activation involved in immune response
## 832  GO:0051250 3.593611e-02  2.897510  1.8292293     5   83                                                                                                     negative regulation of lymphocyte activation
## 833  GO:0043620 2.282418e-02  2.895954  2.2038907     6  100                                                                                  regulation of DNA-templated transcription in response to stress
## 834  GO:0006887 1.189376e-05  2.868337 10.3839442    26  476                                                                                                                                       exocytosis
## 835  GO:0046649 2.398318e-02  2.861005  2.2291667     6  107                                                                                                                            lymphocyte activation
## 837  GO:0006163 4.630907e-03  2.844157  3.7911839    10  173                                                                                                              purine nucleotide metabolic process
## 838  GO:0098657 5.335146e-05  2.841252  8.7162112    22  396                                                                                                                                 import into cell
## 839  GO:0038095 2.488033e-02  2.834899  2.2479685     6  102                                                                                                            Fc-epsilon receptor signaling pathway
## 841  GO:0090263 3.921768e-02  2.824353  1.8733071     5   85                                                                                           positive regulation of canonical Wnt signaling pathway
## 847  GO:0009126 1.606133e-03  2.801512  5.0469096    13  229                                                                                                purine nucleoside monophosphate metabolic process
## 853  GO:0032946 4.092488e-02  2.789130  1.8953460     5   86                                                                                            positive regulation of mononuclear cell proliferation
## 885  GO:0060485 4.447294e-02  2.721230  1.9394238     5   88                                                                                                                           mesenchyme development
## 886  GO:0007596 1.959720e-02  2.720090  2.7348578     7  125                                                                                                                                blood coagulation
## 888  GO:0050792 4.494414e-02  2.712684  1.9451136     5   89                                                                                                                      regulation of viral process
## 894  GO:0061024 1.147556e-03  2.684854  6.1098456    15  284                                                                                                                            membrane organization
## 897  GO:0050865 4.509303e-04  2.663315  7.4491505    18  338                                                                                                                    regulation of cell activation
## 899  GO:0002521 1.505740e-02  2.652756  3.2115869     8  150                                                                                                                        leukocyte differentiation
## 900  GO:0009161 2.525007e-03  2.649942  5.3113765    13  241                                                                                                   ribonucleoside monophosphate metabolic process
## 902  GO:0098771 6.698371e-04  2.645968  7.0524501    17  320                                                                                                                        inorganic ion homeostasis
## 907  GO:0048863 4.971635e-02  2.631579  2.0007414     5   92                                                                                                                        stem cell differentiation
## 932  GO:0045321 7.871821e-04  2.615722  7.1768556    17  356                                                                                                                             leukocyte activation
## 933  GO:0030029 1.651975e-02  2.604921  3.2661290     8  160                                                                                                                     actin filament-based process
## 936  GO:0071453 1.702949e-02  2.588694  3.2837971     8  149                                                                                                               cellular response to oxygen levels
## 940  GO:0098660 1.635568e-03  2.579470  6.3251662    15  287                                                                                                            inorganic ion transmembrane transport
## 941  GO:0022610 3.680986e-05  2.567605 12.4079045    28  563                                                                                                                              biological adhesion
## 942  GO:0097190 3.693089e-02  2.566429  2.4674330     6  115                                                                                                                      apoptotic signaling pathway
## 946  GO:0051251 9.180579e-03  2.551940  4.1873923    10  190                                                                                                     positive regulation of lymphocyte activation
## 947  GO:1902749 1.830996e-02  2.551834  3.3278749     8  151                                                                                                   regulation of cell cycle G2/M phase transition
## 969  GO:0071222 4.276993e-02  2.469679  2.5565132     6  116                                                                                                          cellular response to lipopolysaccharide
## 976  GO:0022407 6.477803e-03  2.442481  5.2672987    12  239                                                                                                                 regulation of cell-cell adhesion
## 977  GO:0019221 3.354479e-02  2.412528  3.0602873     7  158                                                                                                              cytokine-mediated signaling pathway
## 979  GO:0070838 1.416878e-02  2.376062  4.4738981    10  203                                                                                                                     divalent metal ion transport
## 1002 GO:0043488 3.970509e-02  2.318876  3.1736026     7  144                                                                                                                     regulation of mRNA stability
## 1004 GO:0001667 2.967815e-02  2.313393  3.6463189     8  168                                                                                                                    ameboidal-type cell migration
## 1005 GO:0051047 2.235210e-02  2.308982  4.1221976     9  188                                                                                                                 positive regulation of secretion
## 1008 GO:0000902 4.103956e-02  2.302147  3.1976967     7  147                                                                                                                               cell morphogenesis
## 1010 GO:0032880 1.339739e-02  2.291395  5.1137678    11  234                                                                                                               regulation of protein localization
## 1018 GO:0062012 4.238920e-02  2.283929  3.2200526     7  147                                                                                                   regulation of small molecule metabolic process
## 1020 GO:0055082 2.948610e-03  2.276561  8.0882787    17  367                                                                                                                    cellular chemical homeostasis
## 1021 GO:1901988 3.210031e-02  2.275731  3.7025363     8  168                                                                                               negative regulation of cell cycle phase transition
## 1023 GO:0060341 3.259127e-02  2.270081  3.7151305     8  170                                                                                                              regulation of cellular localization
## 1032 GO:0050878 3.495348e-02  2.235337  3.7653023     8  174                                                                                                                  regulation of body fluid levels
## 1037 GO:0010638 4.537207e-03  2.230973  7.7345878    16  355                                                                                                    positive regulation of organelle organization
## 1058 GO:1903311 4.837026e-02  2.213100  3.3161967     7  151                                                                                                             regulation of mRNA metabolic process
## 1061 GO:0098655 3.798613e-02  2.196450  3.8285821     8  177                                                                                                                   cation transmembrane transport
## 1062 GO:0009611 2.970939e-02  2.187793  4.3357819     9  199                                                                                                                             response to wounding
## 1067 GO:0060249 2.411989e-02  2.168317  4.8705984    10  221                                                                                                                 anatomical structure homeostasis
## 1088 GO:0002758 3.628162e-02  2.103529  4.4959370     9  204                                                                                            innate immune response-activating signal transduction
## 1090 GO:0002237 4.909394e-02  2.076658  4.0331199     8  183                                                                                                         response to molecule of bacterial origin
## 1095 GO:1901990 4.922236e-02  2.075910  4.0358034     8  187                                                                                                regulation of mitotic cell cycle phase transition
## 1100 GO:0031347 3.316872e-02  2.048947  5.1393817    10  240                                                                                                                   regulation of defense response
## 1102 GO:0051345 9.475487e-03  2.047209  8.3709677    16  390                                                                                                        positive regulation of hydrolase activity
## 1104 GO:0048534 3.168198e-03  2.038187 11.7590645    22  543                                                                                                      hematopoietic or lymphoid organ development
## 1105 GO:0065008 4.293852e-03  2.037234 11.4000000    21  585                                                                                                                 regulation of biological quality
## 1108 GO:0055086 2.255116e-02  2.033182  6.2470261    12  287                                                                                           nucleobase-containing small molecule metabolic process
## 1110 GO:0051272 2.788066e-02  2.031610  5.7080768    11  259                                                                                               positive regulation of cellular component movement
## 1132 GO:0048729 4.656267e-02  2.000867  4.7115266     9  215                                                                                                                             tissue morphogenesis
## 
## $T$up
##         GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                                   Term
## 129 GO:0006614 3.862499e-26 23.482011  2.0725191    29   93                            SRP-dependent cotranslational protein targeting to membrane
## 130 GO:0000027 2.826412e-08 22.904624  0.5348436     8   24                                                       ribosomal large subunit assembly
## 186 GO:0000184 3.429385e-26 20.181208  2.4833703    31  112                    nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
## 187 GO:0006413 2.948640e-25 19.869170  2.4225230    30  109                                                               translational initiation
## 189 GO:0072599 4.756580e-24 18.987175  2.4067964    29  108                         establishment of protein localization to endoplasmic reticulum
## 190 GO:0019083 8.353178e-24 18.523163  2.4501488    29  111                                                                    viral transcription
## 192 GO:0006612 2.250494e-22 15.032692  2.9774102    30  134                                                          protein targeting to membrane
## 235 GO:0051591 7.807632e-05 14.116071  0.4666091     5   21                                                                       response to cAMP
## 238 GO:0006401 5.453285e-20 11.359833  3.8644408    31  179                                                                  RNA catabolic process
## 285 GO:0016071 1.977650e-18  9.056195  5.0607879    33  244                                                                 mRNA metabolic process
## 286 GO:1902369 1.259190e-04  9.041143  0.8022655     6   36                                           negative regulation of RNA catabolic process
## 372 GO:0010629 5.801281e-15  7.216501  5.7903538    31  293                                                 negative regulation of gene expression
## 373 GO:1903313 4.954618e-05  7.015562  1.3371091     8   60                                          positive regulation of mRNA metabolic process
## 416 GO:0002181 3.883429e-05  6.251435  1.6680641     9   76                                                                cytoplasmic translation
## 457 GO:0042254 1.389625e-03  5.458540  1.2370978     6   57                                                                    ribosome biogenesis
## 502 GO:0046700 6.534522e-14  4.781399 11.4545678    42  514                                                          heterocycle catabolic process
## 503 GO:0044270 7.473209e-14  4.759949 11.4991381    42  516                                           cellular nitrogen compound catabolic process
## 506 GO:0019439 1.113241e-13  4.696673 11.6328491    42  522                                                    aromatic compound catabolic process
## 511 GO:0006518 3.603117e-14  4.615385 12.8555542    45  578                                                              peptide metabolic process
## 512 GO:1901361 2.001101e-13  4.604670 11.8334154    42  531                                              organic cyclic compound catabolic process
## 516 GO:1903312 7.351293e-03  4.483523  1.2256833     5   55                                          negative regulation of mRNA metabolic process
## 522 GO:0009615 7.671680e-03  4.433551  1.2381910     5   56                                                                      response to virus
## 556 GO:0009416 4.969393e-03  4.135035  1.5888293     6   72                                                             response to light stimulus
## 579 GO:0033365 1.093344e-10  3.965396 12.0200698    38  551                                                      protein localization to organelle
## 582 GO:0019538 2.362115e-09  3.903488 12.0387240    35  558                                                              protein metabolic process
## 589 GO:0090092 3.831394e-03  3.808752  2.0056636     7   90 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
## 590 GO:0042752 1.373261e-02  3.795262  1.4262497     5   64                                                         regulation of circadian rhythm
## 591 GO:1903844 1.373261e-02  3.795262  1.4262497     5   64            regulation of cellular response to transforming growth factor beta stimulus
## 618 GO:0006397 1.015106e-02  3.514286  1.8434091     6   86                                                                        mRNA processing
## 669 GO:0002262 8.406957e-03  3.253229  2.3176557     7  104                                                               myeloid cell homeostasis
## 673 GO:0071559 5.791150e-03  3.174932  2.7187885     8  122                                            response to transforming growth factor beta
## 674 GO:0042594 1.569191e-02  3.172008  2.0262246     6   91                                                                 response to starvation
## 699 GO:2001242 1.842102e-02  3.051633  2.0996419     6   95                                    regulation of intrinsic apoptotic signaling pathway
## 702 GO:0061013 3.133659e-03  3.016924  3.5879094    10  161                                                   regulation of mRNA catabolic process
## 705 GO:0009057 3.351213e-02  2.954967  1.7945243     5  103                                                        macromolecule catabolic process
## 727 GO:0043487 5.980468e-03  2.915656  3.3204876     9  149                                                            regulation of RNA stability
## 760 GO:0009617 3.941602e-03  2.749105  4.3165360    11  196                                                                  response to bacterium
## 770 GO:0042770 4.817803e-02  2.657265  1.9833785     5   89                                          signal transduction in response to DNA damage
## 772 GO:0071216 2.268635e-02  2.634104  2.8180473     7  127                                                   cellular response to biotic stimulus
## 808 GO:0043207 2.109608e-04  2.452093 10.9197242    24  490                                                   response to external biotic stimulus
## 841 GO:0002683 1.183066e-02  2.334105  5.0195182    11  227                                           negative regulation of immune system process
## 855 GO:0045861 3.003290e-02  2.307692  3.6547648     8  164                                                     negative regulation of proteolysis
## 857 GO:0006364 2.307242e-02  2.295231  4.1450382     9  186                                                                        rRNA processing
## 862 GO:0071495 1.858212e-02  2.272090  4.6730619    10  217                                               cellular response to endogenous stimulus
## 867 GO:0000122 9.911414e-04  2.255436 10.7191578    22  481                              negative regulation of transcription by RNA polymerase II
## 869 GO:2001234 4.582091e-02  2.241667  3.2759173     7  147                                     negative regulation of apoptotic signaling pathway
## 895 GO:0009895 3.097417e-02  2.169693  4.3678897     9  196                                               negative regulation of catabolic process
## 896 GO:0070925 1.173537e-02  2.166522  6.3997985    13  292                                                                     organelle assembly
## 901 GO:0051094 1.320790e-02  2.131585  6.5001281    13  295                                           positive regulation of developmental process
## 
## 
## $NK
## $NK$down
##          GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                                                                                             Term
## 200  GO:0034314 2.577609e-07 34.763158  0.3055110     6   14                                                                                                         Arp2/3 complex-mediated actin nucleation
## 286  GO:0001916 1.763484e-05 20.721003  0.3526225     5   16                                                                                              positive regulation of T cell mediated cytotoxicity
## 307  GO:0002252 4.050244e-08 15.824176  0.7531585     9   44                                                                                                                          immune effector process
## 323  GO:0031343 3.983090e-07 14.891294  0.7239339     8   33                                                                                                              positive regulation of cell killing
## 389  GO:1903307 1.198382e-04 12.651660  0.5068949     5   23                                                                                               positive regulation of regulated secretory pathway
## 390  GO:0035722 2.003636e-06 11.565789  0.8815563     8   40                                                                                                        interleukin-12-mediated signaling pathway
## 391  GO:0070527 8.964338e-06 11.504360  0.7713617     7   35                                                                                                                             platelet aggregation
## 463  GO:0070671 3.570570e-06 10.570426  0.9476730     8   43                                                                                                                       response to interleukin-12
## 467  GO:0038096 7.969003e-08 10.187625  1.3596156    11   62                                                                                     Fc-gamma receptor signaling pathway involved in phagocytosis
## 468  GO:0006968 7.114581e-05 10.168272  0.7272839     6   33                                                                                                                        cellular defense response
## 469  GO:0032535 3.276949e-11 10.137902  2.1674141    17  100                                                                                                            regulation of cellular component size
## 475  GO:0048013 1.375506e-06  9.959244  1.1239842     9   51                                                                                                                ephrin receptor signaling pathway
## 476  GO:0001910 8.045137e-05  9.903509  0.7422299     6   34                                                                                                    regulation of leukocyte mediated cytotoxicity
## 556  GO:0006909 7.290724e-07  7.912120  1.6739320    11   80                                                                                                                                     phagocytosis
## 558  GO:0098609 2.970652e-06  7.648003  1.5589247    10   76                                                                                                                               cell-cell adhesion
## 563  GO:0007229 9.750162e-05  7.518836  1.0961941     7   50                                                                                                              integrin-mediated signaling pathway
## 570  GO:0002708 3.121726e-04  7.475581  0.9399778     6   43                                                                                              positive regulation of lymphocyte mediated immunity
## 616  GO:0032760 3.999112e-04  7.098516  0.9826055     6   45                                                                                          positive regulation of tumor necrosis factor production
## 617  GO:0002479 1.614627e-05  7.074377  1.4986457     9   68                                                  antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
## 627  GO:0050777 1.687850e-03  6.532392  0.8765631     5   40                                                                                                           negative regulation of immune response
## 677  GO:0060337 1.917364e-03  6.327071  0.9015442     5   41                                                                                                              type I interferon signaling pathway
## 678  GO:0002253 5.444856e-10  6.311685  4.0854322    21  191                                                                                                                    activation of immune response
## 679  GO:0006955 6.862053e-04  6.280495  1.0783437     6   74                                                                                                                                  immune response
## 681  GO:0050776 1.927652e-03  6.271360  0.8989630     5   49                                                                                                                    regulation of immune response
## 683  GO:0002824 2.317068e-03  6.029682  0.9399778     5   43 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
## 684  GO:0051258 1.548954e-08  6.012594  3.5923418    18  163                                                                                                                           protein polymerization
## 685  GO:1903555 8.407633e-06  5.981935  2.1377739    11   97                                                                              regulation of tumor necrosis factor superfamily cytokine production
## 697  GO:0045454 1.131431e-03  5.704480  1.1901010     6   54                                                                                                                           cell redox homeostasis
## 698  GO:0097581 2.941703e-03  5.677443  0.9917508     5   45                                                                                                                       lamellipodium organization
## 741  GO:0006521 3.485808e-03  5.435590  1.0304225     5   47                                                                                              regulation of cellular amino acid metabolic process
## 743  GO:0002709 3.564990e-03  5.405720  1.0358286     5   47                                                                                                           regulation of T cell mediated immunity
## 749  GO:0031334 2.093736e-06  5.292120  3.0705548    14  142                                                                                                  positive regulation of protein complex assembly
## 755  GO:0002576 1.706704e-03  5.222112  1.2864006     6   59                                                                                                                           platelet degranulation
## 756  GO:0044106 4.144488e-03  5.199524  1.0719318     5   49                                                                                                                 cellular amine metabolic process
## 761  GO:0098869 4.277870e-03  5.158699  1.0799064     5   49                                                                                                                  cellular oxidant detoxification
## 762  GO:0002443 4.301010e-03  5.120523  1.0777501     5   60                                                                                                                      leukocyte mediated immunity
## 764  GO:0043312 3.623034e-12  5.087890  8.1776081    33  373                                                                                                                         neutrophil degranulation
## 780  GO:0002275 1.771410e-12  4.965972  8.9449440    35  408                                                                                              myeloid cell activation involved in immune response
## 804  GO:0042119 1.858346e-11  4.884769  8.1823225    32  375                                                                                                                            neutrophil activation
## 806  GO:1903900 5.875300e-03  4.751696  1.1623095     5   53                                                                                                                   regulation of viral life cycle
## 819  GO:0009615 6.808876e-03  4.570045  1.2030151     5   56                                                                                                                                response to virus
## 820  GO:0032091 6.880405e-03  4.559538  1.2062592     5   55                                                                                                           negative regulation of protein binding
## 822  GO:0002444 6.386064e-10  4.541011  7.8179903    29  369                                                                                                              myeloid leukocyte mediated immunity
## 823  GO:0032981 7.020777e-03  4.536207  1.2121399     5   55                                                                                               mitochondrial respiratory chain complex I assembly
## 864  GO:0002263 1.726379e-12  4.444643 11.5263482    40  523                                                                                                      cell activation involved in immune response
## 865  GO:1901657 3.696821e-03  4.415041  1.4967231     6   68                                                                                                              glycosyl compound metabolic process
## 867  GO:0045055 7.303549e-10  4.396238  8.3929685    30  408                                                                                                                             regulated exocytosis
## 868  GO:0002685 8.943513e-04  4.393838  2.0204812     8   92                                                                                                                regulation of leukocyte migration
## 869  GO:0051924 7.968357e-03  4.387299  1.2491024     5   57                                                                                                              regulation of calcium ion transport
## 871  GO:0048525 4.002489e-03  4.338013  1.5206846     6   69                                                                                                             negative regulation of viral process
## 872  GO:0060071 4.002489e-03  4.338013  1.5206846     6   69                                                                                              Wnt signaling pathway, planar cell polarity pathway
## 876  GO:0043900 2.128190e-03  4.267184  1.8077020     7   84                                                                                                             regulation of multi-organism process
## 881  GO:0019884 8.014101e-05  4.219531  3.1956415    12  145                                                                                         antigen processing and presentation of exogenous antigen
## 882  GO:0060402 9.241678e-03  4.218583  1.2943061     5   59                                                                                                               calcium ion transport into cytosol
## 884  GO:0048002 8.153717e-05  4.211113  3.2012811    12  146                                                                                           antigen processing and presentation of peptide antigen
## 886  GO:0034340 4.612298e-03  4.203468  1.5647624     6   71                                                                                                                    response to type I interferon
## 888  GO:0098754 9.417587e-03  4.198063  1.3002955     5   59                                                                                                                                   detoxification
## 890  GO:0007163 6.242855e-04  4.171953  2.3917653     9  109                                                                                                    establishment or maintenance of cell polarity
## 892  GO:0002758 4.925464e-03  4.143316  1.5859825     6   72                                                                                            innate immune response-activating signal transduction
## 898  GO:0050900 1.050025e-02  4.073060  1.3341705     5   64                                                                                                                              leukocyte migration
## 910  GO:0002764 3.665829e-09  4.052013  8.9477961    30  406                                                                                                     immune response-regulating signaling pathway
## 926  GO:0002429 1.874457e-05  4.043940  4.2072307    15  204                                                                               immune response-activating cell surface receptor signaling pathway
## 929  GO:0051897 5.651799e-03  4.016491  1.6308791     6   74                                                                                                positive regulation of protein kinase B signaling
## 930  GO:0098657 8.195315e-09  3.999744  8.7162112    29  396                                                                                                                                 import into cell
## 934  GO:0001736 6.033583e-03  3.957778  1.6529180     6   75                                                                                                                 establishment of planar polarity
## 935  GO:0046649 6.193462e-03  3.930638  1.6609470     6   82                                                                                                                            lymphocyte activation
## 937  GO:0008360 3.384773e-03  3.901517  1.9614627     7   89                                                                                                                         regulation of cell shape
## 938  GO:0042773 6.433842e-03  3.900743  1.6749569     6   76                                                                                                         ATP synthesis coupled electron transport
## 966  GO:0050852 1.445337e-03  3.667241  2.6888367     9  125                                                                                                                T cell receptor signaling pathway
## 967  GO:0051651 1.579071e-02  3.652670  1.4766067     5   67                                                                                                                  maintenance of location in cell
## 976  GO:0022900 1.711083e-03  3.572160  2.7548633     9  125                                                                                                                         electron transport chain
## 978  GO:0045580 1.757773e-02  3.546785  1.5170455     5   69                                                                                                             regulation of T cell differentiation
## 981  GO:0031145 1.774441e-02  3.537626  1.5206846     5   69                                                                                           anaphase-promoting complex-dependent catabolic process
## 983  GO:0002223 1.036043e-02  3.497110  1.8512682     6   84                                                                                             stimulatory C-type lectin receptor signaling pathway
## 984  GO:0052547 8.818176e-05  3.487324  4.8044817    15  218                                                                                                                 regulation of peptidase activity
## 985  GO:1903039 1.171351e-03  3.485119  3.1427867    10  144                                                                                              positive regulation of leukocyte cell-cell adhesion
## 987  GO:0010950 3.594056e-03  3.458899  2.5124354     8  114                                                                                                    positive regulation of endopeptidase activity
## 1012 GO:0050817 2.239496e-03  3.423302  2.8643607     9  131                                                                                                                                      coagulation
## 1021 GO:0061572 2.211723e-02  3.327840  1.6088402     5   73                                                                                                               actin filament bundle organization
## 1023 GO:0007599 2.746472e-03  3.313350  2.9514575     9  135                                                                                                                                       hemostasis
## 1027 GO:0010638 1.158445e-04  3.249544  5.4955519    16  258                                                                                                    positive regulation of organelle organization
## 1029 GO:2000116 1.989528e-03  3.227542  3.3719527    10  153                                                                                               regulation of cysteine-type endopeptidase activity
## 1031 GO:0051050 5.402824e-03  3.215893  2.6877333     8  133                                                                                                                 positive regulation of transport
## 1033 GO:0042060 1.275829e-03  3.213680  3.7391304    11  172                                                                                                                                    wound healing
## 1038 GO:1905330 1.498702e-02  3.206256  2.0055405     6   91                                                                                                     regulation of morphogenesis of an epithelium
## 1063 GO:0033209 2.722883e-02  3.137867  1.6983793     5   78                                                                                                 tumor necrosis factor-mediated signaling pathway
## 1068 GO:0065008 7.090336e-06  3.092243  9.6051617    25  502                                                                                                                 regulation of biological quality
## 1070 GO:0017157 2.911605e-02  3.078039  1.7286085     5   80                                                                                                                         regulation of exocytosis
## 1072 GO:0002244 1.115844e-02  3.067587  2.4463186     7  111                                                                                                    hematopoietic progenitor cell differentiation
## 1078 GO:0010951 1.906238e-02  3.026204  2.1157350     6   96                                                                                                    negative regulation of endopeptidase activity
## 1080 GO:0051235 1.929480e-02  3.017081  2.1214232     6   98                                                                                                                          maintenance of location
## 1082 GO:0045087 1.222947e-02  3.009736  2.4905072     7  126                                                                                                                           innate immune response
## 1083 GO:0046034 1.953810e-02  3.008152  2.1275109     6   98                                                                                                                            ATP metabolic process
## 1103 GO:1902105 1.310538e-02  2.965850  2.5241815     7  115                                                                                                          regulation of leukocyte differentiation
## 1104 GO:2000045 3.332731e-02  2.961341  1.7922944     5   82                                                                                              regulation of G1/S transition of mitotic cell cycle
## 1108 GO:0051224 2.184044e-02  2.927466  2.1818518     6   99                                                                                                         negative regulation of protein transport
## 1110 GO:0001667 3.981159e-03  2.909431  3.7097768    10  170                                                                                                                    ameboidal-type cell migration
## 1111 GO:0055074 2.653833e-03  2.906395  4.0992366    11  186                                                                                                                          calcium ion homeostasis
## 1113 GO:0030030 3.697259e-02  2.875791  1.8441368     5   85                                                                                                                     cell projection organization
## 1118 GO:0070374 3.755483e-02  2.860468  1.8512682     5   84                                                                                                     positive regulation of ERK1 and ERK2 cascade
## 1121 GO:0038095 2.488033e-02  2.834899  2.2479685     6  102                                                                                                            Fc-epsilon receptor signaling pathway
## 1123 GO:0043207 3.386031e-04  2.827786  6.6512155    17  307                                                                                                             response to external biotic stimulus
## 1131 GO:0061024 3.737957e-04  2.802177  6.7091161    17  313                                                                                                                            membrane organization
## 1140 GO:0051271 1.157912e-02  2.789875  3.0634080     8  139                                                                                               negative regulation of cellular component movement
## 1141 GO:0032946 4.092488e-02  2.789130  1.8953460     5   86                                                                                            positive regulation of mononuclear cell proliferation
## 1142 GO:0001817 4.111978e-02  2.784091  1.8974721     5   93                                                                                                                regulation of cytokine production
## 1161 GO:0001666 2.475590e-03  2.781916  4.6722482    12  212                                                                                                                              response to hypoxia
## 1162 GO:0098660 5.744504e-04  2.778892  6.3251662    16  287                                                                                                            inorganic ion transmembrane transport
## 1164 GO:0070588 1.801736e-02  2.770273  2.6887466     7  122                                                                                                              calcium ion transmembrane transport
## 1166 GO:0030336 4.245082e-02  2.758754  1.9144623     5   88                                                                                                            negative regulation of cell migration
## 1168 GO:0090132 1.254853e-02  2.747219  3.1074858     8  141                                                                                                                             epithelium migration
## 1170 GO:0051046 2.285639e-04  2.746984  7.6743040    19  350                                                                                                                          regulation of secretion
## 1179 GO:0072503 6.973076e-03  2.666873  4.0204888    10  183                                                                                                   cellular divalent inorganic cation homeostasis
## 1181 GO:0051607 3.239078e-02  2.653381  2.3910026     6  109                                                                                                                        defense response to virus
## 1191 GO:0040013 1.581497e-02  2.626614  3.2397193     8  147                                                                                                                negative regulation of locomotion
## 1210 GO:2000027 3.433270e-02  2.614162  2.4242797     6  110                                                                                                         regulation of animal organ morphogenesis
## 1215 GO:0030335 1.177446e-02  2.594755  3.6996146     9  172                                                                                                            positive regulation of cell migration
## 1217 GO:0009126 4.631391e-03  2.558349  5.0469096    12  229                                                                                                purine nucleoside monophosphate metabolic process
## 1221 GO:0006875 3.587033e-03  2.535309  5.5317656    13  251                                                                                                                   cellular metal ion homeostasis
## 1222 GO:0009199 5.134189e-03  2.522482  5.1130263    12  232                                                                                                    ribonucleoside triphosphate metabolic process
## 1223 GO:0051251 3.998051e-02  2.513352  2.5147223     6  117                                                                                                     positive regulation of lymphocyte activation
## 1228 GO:0009144 5.492966e-03  2.499110  5.1571042    12  234                                                                                                 purine nucleoside triphosphate metabolic process
## 1230 GO:0051270 1.629538e-03  2.498065  6.9830891    16  326                                                                                                        regulation of cellular component movement
## 1236 GO:0051098 5.679702e-03  2.487581  5.1791431    12  235                                                                                                                            regulation of binding
## 1237 GO:0070482 5.679702e-03  2.487581  5.1791431    12  235                                                                                                                        response to oxygen levels
## 1257 GO:0060759 4.276993e-02  2.469679  2.5565132     6  116                                                                                                      regulation of response to cytokine stimulus
## 1258 GO:0071222 4.276993e-02  2.469679  2.5565132     6  116                                                                                                          cellular response to lipopolysaccharide
## 1266 GO:0009161 6.908875e-03  2.420521  5.3113765    12  241                                                                                                   ribonucleoside monophosphate metabolic process
## 1270 GO:0036294 3.374241e-02  2.408254  3.0634080     7  139                                                                                                     cellular response to decreased oxygen levels
## 1271 GO:0040012 7.226431e-03  2.407710  5.3461976    12  253                                                                                                                         regulation of locomotion
## 1273 GO:0045785 9.812907e-03  2.402342  4.8875740    11  224                                                                                                             positive regulation of cell adhesion
## 1279 GO:0072521 4.188410e-03  2.395435  6.3001867    14  286                                                                                                     purine-containing compound metabolic process
## 1283 GO:0007264 3.484282e-02  2.391291  3.0852537     7  140                                                                                                        small GTPase mediated signal transduction
## 1285 GO:0070838 1.416878e-02  2.376062  4.4738981    10  203                                                                                                                     divalent metal ion transport
## 1287 GO:0098771 3.496799e-03  2.366921  6.8444664    15  312                                                                                                                        inorganic ion homeostasis
## 1315 GO:0001775 9.901613e-03  2.311401  5.5883212    12  319                                                                                                                                  cell activation
## 1317 GO:0070201 4.078413e-02  2.305288  3.1931166     7  150                                                                                              regulation of establishment of protein localization
## 1318 GO:0051130 1.736598e-02  2.299943  4.6247062    10  233                                                                                           positive regulation of cellular component organization
## 1327 GO:0055082 2.948610e-03  2.276561  8.0882787    17  367                                                                                                                    cellular chemical homeostasis
## 1338 GO:0051240 1.191970e-03  2.228533 10.9013401    22  524                                                                                          positive regulation of multicellular organismal process
## 1360 GO:0090087 2.966891e-03  2.219005  8.7935238    18  399                                                                                                                  regulation of peptide transport
## 1363 GO:0042592 5.392836e-04  2.215738 13.0970724    26  600                                                                                                                              homeostatic process
## 1375 GO:0060341 2.780636e-03  2.138695 10.1682776    20  461                                                                                                              regulation of cellular localization
## 1379 GO:0007186 4.391635e-02  2.128514  3.9422383     8  182                                                                                                     G protein-coupled receptor signaling pathway
## 1393 GO:0010942 7.599793e-03  2.101397  8.1697902    16  374                                                                                                                positive regulation of cell death
## 1399 GO:0002790 3.184333e-02  2.063300  5.1023573    10  235                                                                                                                                peptide secretion
## 1400 GO:0045862 3.308816e-02  2.048452  5.1350653    10  233                                                                                                               positive regulation of proteolysis
## 1422 GO:0019693 1.372826e-02  2.001600  7.9812762    15  364                                                                                                               ribose phosphate metabolic process
## 
## $NK$up
##         GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                Term
## 57  GO:0006614 7.310233e-59 69.290981  2.0152672    49   93         SRP-dependent cotranslational protein targeting to membrane
## 58  GO:0019083 1.046886e-55 51.751719  2.3950893    50  111                                                 viral transcription
## 59  GO:0072599 1.269234e-54 51.576538  2.3403103    49  108      establishment of protein localization to endoplasmic reticulum
## 103 GO:0000184 1.090790e-52 45.372077  2.5136666    49  116 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
## 104 GO:0006612 1.408592e-50 37.342857  2.8947044    50  134                                       protein targeting to membrane
## 108 GO:0006413 1.269785e-44 27.393894  3.4546576    49  160                                            translational initiation
## 156 GO:0000027 5.049409e-07 19.318830  0.5200689     7   24                                    ribosomal large subunit assembly
## 205 GO:0002181 1.572191e-13 14.963571  1.5880612    17   74                                             cytoplasmic translation
## 206 GO:0006401 6.726316e-36 14.775377  5.9004093    52  275                                               RNA catabolic process
## 262 GO:0019222 4.756282e-18  9.270877  6.5167883    35  372                                     regulation of metabolic process
## 294 GO:0034097 1.531653e-04  8.645866  0.8280683     6   40                                                response to cytokine
## 297 GO:1901575 1.789018e-24  8.023189 10.0979303    52  469                                 organic substance catabolic process
## 300 GO:0006518 2.734918e-27  7.659931 12.4984555    61  578                                           peptide metabolic process
## 339 GO:0016071 1.152937e-24  7.089018 12.5580235    58  592                                              mRNA metabolic process
## 427 GO:0006364 1.931213e-07  5.296667  3.7757367    17  175                                                     rRNA processing
## 519 GO:1903313 9.424440e-03  4.195109  1.3001724     5   60                       positive regulation of mRNA metabolic process
## 521 GO:0032496 9.510776e-03  4.184058  1.3028978     5   61                                      response to lipopolysaccharide
## 596 GO:0071826 6.206677e-05  3.608385  4.6589510    15  215                      ribonucleoprotein complex subunit organization
## 641 GO:0002262 7.252144e-03  3.351613  2.2536321     7  104                                            myeloid cell homeostasis
## 643 GO:2001235 7.904819e-03  3.293350  2.2904062     7  106                  positive regulation of apoptotic signaling pathway
## 646 GO:0042770 2.384203e-02  3.257249  1.6401529     5   76                       signal transduction in response to DNA damage
## 671 GO:0050821 5.404164e-03  3.214286  2.6870229     8  124                                               protein stabilization
## 701 GO:0017148 3.337144e-02  2.959653  1.7927672     5   83                                  negative regulation of translation
## 707 GO:0070374 3.530478e-02  2.911763  1.8202413     5   84                        positive regulation of ERK1 and ERK2 cascade
## 709 GO:0009617 2.761967e-03  2.891310  4.1214383    11  196                                               response to bacterium
## 749 GO:0048017 4.538911e-02  2.704162  1.9502586     5   90                                   inositol lipid-mediated signaling
## 776 GO:0043207 5.030862e-05  2.663605 10.6180744    25  490                                response to external biotic stimulus
## 781 GO:0071902 8.195142e-03  2.599063  4.1172125    10  190     positive regulation of protein serine/threonine kinase activity
## 818 GO:0030522 2.245198e-02  2.449642  3.4568115     8  161                            intracellular receptor signaling pathway
## 820 GO:0043066 4.873352e-03  2.440438  5.7414906    13  275                            negative regulation of apoptotic process
## 838 GO:0045861 2.597650e-02  2.377900  3.5538045     8  164                                  negative regulation of proteolysis
## 858 GO:0045944 3.853770e-04  2.268452 12.8013589    26  599           positive regulation of transcription by RNA polymerase II
## 885 GO:0034660 2.248810e-03  2.230125  9.2745629    19  428                                             ncRNA metabolic process
## 909 GO:0060548 4.145299e-03  2.146274  9.0848856    18  430                                   negative regulation of cell death
## 922 GO:0000122 3.683310e-03  2.081595 10.4230485    20  481           negative regulation of transcription by RNA polymerase II
## 940 GO:0070925 1.235069e-02  2.030903  7.8862701    15  372                                                  organelle assembly
## 
## 
## $B
## $B$down
##          GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                                                                      Term
## 105  GO:0034314 2.250493e-07 35.613772  0.2986068     6   14                                                                                  Arp2/3 complex-mediated actin nucleation
## 163  GO:0050853 6.061918e-08 20.050729  0.5801432     8   27                                                                                         B cell receptor signaling pathway
## 217  GO:0035722 1.689926e-06 11.848802  0.8618567     8   40                                                                                 interleukin-12-mediated signaling pathway
## 260  GO:0070671 3.015507e-06 10.829085  0.9264959     8   43                                                                                                response to interleukin-12
## 262  GO:0038093 2.430486e-07 10.442928  1.2011222    10   57                                                                                             Fc receptor signaling pathway
## 263  GO:0032535 2.475623e-11 10.339384  2.1300448    17  100                                                                                     regulation of cellular component size
## 268  GO:0002252 7.866883e-08 10.128392  1.3516439    11   74                                                                                                   immune effector process
## 318  GO:0048013 1.143241e-05  8.805459  1.0988673     8   51                                                                                         ephrin receptor signaling pathway
## 320  GO:0002449 4.711954e-05  8.532344  0.9801449     7   47                                                                                              lymphocyte mediated immunity
## 328  GO:0045454 1.767995e-05  8.228066  1.1635065     8   54                                                                                                    cell redox homeostasis
## 330  GO:0038096 5.938276e-06  8.120069  1.3290625     9   62                                                              Fc-gamma receptor signaling pathway involved in phagocytosis
## 331  GO:0032956 6.844509e-09  8.054177  2.2930221    15  108                                                                             regulation of actin cytoskeleton organization
## 332  GO:0070527 8.429152e-04  7.761765  0.7541246     5   35                                                                                                      platelet aggregation
## 375  GO:0030183 2.977594e-04  7.533971  0.9309577     6   44                                                                                                    B cell differentiation
## 376  GO:0032943 1.042135e-04  7.410870  1.1056839     7   53                                                                                            mononuclear cell proliferation
## 378  GO:0050766 1.363249e-03  6.882179  0.8360232     5   39                                                                                       positive regulation of phagocytosis
## 379  GO:0034765 1.841498e-04  6.698528  1.2083801     7   57                                                                                 regulation of ion transmembrane transport
## 393  GO:0002253 3.088878e-10  6.536693  3.9645614    21  191                                                                                             activation of immune response
## 425  GO:0060337 1.734690e-03  6.480112  0.8812847     5   41                                                                                       type I interferon signaling pathway
## 427  GO:0002479 9.718760e-05  6.297006  1.4651564     8   68                           antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
## 433  GO:0031334 1.304847e-06  6.010205  2.5363073    13  119                                                                           positive regulation of protein complex assembly
## 438  GO:0019886 1.324089e-04  5.994867  1.5297956     8   71                                         antigen processing and presentation of exogenous peptide antigen via MHC class II
## 443  GO:0048584 2.512184e-10  5.766667  5.2222222    24  264                                                                               positive regulation of response to stimulus
## 446  GO:0051258 6.669386e-08  5.748960  3.5120660    17  163                                                                                                    protein polymerization
## 447  GO:0002250 7.003133e-05  5.737500  1.7932250     9   89                                                                                                  adaptive immune response
## 471  GO:0006909 7.778460e-05  5.654116  1.8175936     9   88                                                                                                              phagocytosis
## 472  GO:0002429 3.077802e-11  5.616730  5.9683575    27  277                                                        immune response-activating cell surface receptor signaling pathway
## 476  GO:0098754 1.606547e-03  5.287931  1.2712386     6   59                                                                                                            detoxification
## 477  GO:0002504 6.840134e-04  5.276439  1.4915630     7   70                                 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II
## 479  GO:0006959 1.724426e-03  5.204628  1.2880958     6   61                                                                                                   humoral immune response
## 480  GO:0006521 4.242904e-03  5.164706  1.0773209     5   50                                                                       regulation of cellular amino acid metabolic process
## 481  GO:0002460 4.270743e-03  5.149333  1.0781914     5   52 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
## 484  GO:1902600 1.873431e-03  5.115584  1.3092389     6   61                                                                                            proton transmembrane transport
## 523  GO:0002474 1.043439e-03  4.879164  1.6000740     7   75                                                    antigen processing and presentation of peptide antigen via MHC class I
## 525  GO:0002478 2.408688e-03  4.838849  1.3736332     6   67                                                          antigen processing and presentation of exogenous peptide antigen
## 526  GO:0051130 5.062075e-04  4.827175  1.8555467     8   93                                                                    positive regulation of cellular component organization
## 532  GO:0060402 6.129486e-03  4.694643  1.1732429     5   55                                                                                        calcium ion transport into cytosol
## 533  GO:0019882 1.281192e-03  4.691169  1.6555334     7   81                                                                                       antigen processing and presentation
## 538  GO:0022900 7.490378e-05  4.608633  2.6933021    11  125                                                                                                  electron transport chain
## 573  GO:0031145 3.581638e-03  4.442942  1.4867028     6   69                                                                    anaphase-promoting complex-dependent catabolic process
## 576  GO:0060333 3.848907e-03  4.372966  1.5082492     6   70                                                                               interferon-gamma-mediated signaling pathway
## 579  GO:0098609 1.911971e-03  4.353422  1.7739883     7   85                                                                                                        cell-cell adhesion
## 580  GO:0034340 4.130695e-03  4.305143  1.5297956     6   71                                                                                             response to type I interferon
## 587  GO:0002764 2.104463e-09  4.165994  8.7478454    30  406                                                                              immune response-regulating signaling pathway
## 618  GO:0016999 6.003360e-03  3.959759  1.6506098     6   77                                                                                              antibiotic metabolic process
## 621  GO:0033209 6.518920e-03  3.887401  1.6790795     6   78                                                                          tumor necrosis factor-mediated signaling pathway
## 624  GO:0002684 7.959149e-09  3.832508  9.8491042    31  476                                                                              positive regulation of immune system process
## 629  GO:0043900 3.840052e-03  3.804842  2.0057811     7   95                                                                                      regulation of multi-organism process
## 649  GO:0045055 7.933682e-08  3.658200  9.0943021    28  425                                                                                                      regulated exocytosis
## 650  GO:0002275 1.333342e-07  3.646473  8.7439340    27  408                                                                       myeloid cell activation involved in immune response
## 652  GO:0002444 3.738804e-07  3.634370  8.0602499    25  381                                                                                       myeloid leukocyte mediated immunity
## 653  GO:0050852 8.781753e-04  3.630609  3.0270204    10  141                                                                                         T cell receptor signaling pathway
## 654  GO:0051235 4.910157e-03  3.624709  2.0970391     7   98                                                                                                   maintenance of location
## 655  GO:0060071 1.624234e-02  3.622702  1.4867028     5   69                                                                       Wnt signaling pathway, planar cell polarity pathway
## 657  GO:0009308 1.690316e-02  3.583068  1.5016644     5   70                                                                                                   amine metabolic process
## 659  GO:0072593 2.954430e-03  3.580034  2.4337170     8  113                                                                                 reactive oxygen species metabolic process
## 661  GO:0062012 9.638646e-03  3.555727  1.8228838     6   85                                                                            regulation of small molecule metabolic process
## 669  GO:0045321 7.288544e-06  3.521102  6.5522447    20  335                                                                                                      leukocyte activation
## 690  GO:0032946 1.041688e-02  3.491272  1.8529919     6   86                                                                     positive regulation of mononuclear cell proliferation
## 692  GO:0002700 1.099416e-02  3.447732  1.8745383     6   87                                                         regulation of production of molecular mediator of immune response
## 693  GO:0043312 1.518767e-06  3.429410  8.1014528    24  376                                                                                                  neutrophil degranulation
## 694  GO:0070663 2.248484e-03  3.420472  2.8656735     9  133                                                                                     regulation of leukocyte proliferation
## 696  GO:0002263 5.663606e-08  3.398117 11.2687762    32  523                                                                               cell activation involved in immune response
## 701  GO:0042119 2.307617e-06  3.339950  8.2953706    24  385                                                                                                     neutrophil activation
## 705  GO:0001736 2.251881e-02  3.309664  1.6159813     5   75                                                                                          establishment of planar polarity
## 712  GO:0098660 4.315780e-05  3.272417  6.1838217    18  287                                                                                     inorganic ion transmembrane transport
## 715  GO:0042773 2.369804e-02  3.262635  1.6375277     5   76                                                                                  ATP synthesis coupled electron transport
## 732  GO:0002521 8.172597e-04  3.205571  4.1064629    12  194                                                                                                 leukocyte differentiation
## 733  GO:1903706 2.158449e-03  3.190212  3.4101342    10  159                                                                                                 regulation of hemopoiesis
## 738  GO:0032940 5.356758e-06  3.097913  9.3426058    25  443                                                                                                         secretion by cell
## 748  GO:0034764 3.018993e-02  3.046053  1.7452598     5   81                                                                            positive regulation of transmembrane transport
## 765  GO:0006874 2.987240e-03  3.038568  3.5641500    10  167                                                                                          cellular calcium ion homeostasis
## 766  GO:0048871 1.173825e-02  3.034795  2.4702366     7  116                                                                                      multicellular organismal homeostasis
## 767  GO:0060249 1.893626e-02  3.030153  2.1122360     6  100                                                                                          anatomical structure homeostasis
## 775  GO:0071345 1.083652e-03  2.946677  4.8440581    13  254                                                                                    cellular response to cytokine stimulus
## 779  GO:0002223 3.457392e-02  2.929263  1.8098990     5   84                                                                      stimulatory C-type lectin receptor signaling pathway
## 782  GO:0072507 1.745498e-03  2.911356  4.4816548    12  208                                                                                     divalent inorganic cation homeostasis
## 784  GO:0038095 2.256059e-02  2.903476  2.1977345     6  102                                                                                     Fc-epsilon receptor signaling pathway
## 785  GO:0030100 6.209547e-03  2.896889  3.3396947     9  155                                                                                                 regulation of endocytosis
## 793  GO:0010959 1.552403e-02  2.860136  2.6095450     7  122                                                                                         regulation of metal ion transport
## 815  GO:0009607 3.273015e-04  2.837898  6.6337246    17  311                                                                                               response to biotic stimulus
## 819  GO:0006873 5.405293e-04  2.796828  6.2915538    16  292                                                                                                  cellular ion homeostasis
## 820  GO:0097237 1.725583e-02  2.795640  2.6651467     7  125                                                                                      cellular response to toxic substance
## 824  GO:0042180 1.196669e-02  2.772056  3.0811377     8  143                                                                                         cellular ketone metabolic process
## 827  GO:0002831 4.271836e-02  2.753151  1.9176311     5   89                                                                                 regulation of response to biotic stimulus
## 833  GO:0072511 4.523822e-03  2.694743  4.3954691    11  204                                                                                       divalent inorganic cation transport
## 839  GO:1905330 4.627370e-02  2.688440  1.9607240     5   91                                                                              regulation of morphogenesis of an epithelium
## 859  GO:0098655 2.413617e-03  2.666381  5.2861744    13  251                                                                                            cation transmembrane transport
## 861  GO:0045619 4.840683e-02  2.652192  1.9855609     5   93                                                                                  regulation of lymphocyte differentiation
## 862  GO:0002244 3.244626e-02  2.651564  2.3916523     6  111                                                                             hematopoietic progenitor cell differentiation
## 888  GO:1903039 1.932803e-02  2.524357  3.3612411     8  156                                                                       positive regulation of leukocyte cell-cell adhesion
## 901  GO:0050878 3.321859e-02  2.416934  3.0531281     7  143                                                                                           regulation of body fluid levels
## 918  GO:0007596 3.624460e-02  2.368567  3.1109741     7  145                                                                                                         blood coagulation
## 928  GO:0010638 2.387534e-03  2.329404  7.9297010    17  371                                                                             positive regulation of organelle organization
## 956  GO:0050867 1.873566e-02  2.266140  4.6755725    10  217                                                                                    positive regulation of cell activation
## 972  GO:0032879 1.880473e-02  2.176833  5.3862389    11  264                                                                                                regulation of localization
## 980  GO:0002758 3.206153e-02  2.155329  4.3954691     9  204                                                                     innate immune response-activating signal transduction
## 988  GO:0019725 8.987420e-03  2.115786  7.6031904    15  372                                                                                                      cellular homeostasis
## 996  GO:0070482 3.044516e-02  2.080000  5.0634080    10  235                                                                                                 response to oxygen levels
## 1013 GO:0001666 3.951471e-02  2.068253  4.5678404     9  212                                                                                                       response to hypoxia
## 
## $B$up
##         GOBPID       Pvalue OddsRatio   ExpCount Count Size                                                                     Term
## 325 GO:0006614 6.394067e-09  8.943687  1.9465649    14   93              SRP-dependent cotranslational protein targeting to membrane
## 379 GO:0006413 4.571773e-08  7.505194  2.2601192    14  109                                                 translational initiation
## 380 GO:0072599 4.587626e-08  7.502182  2.2605270    14  108           establishment of protein localization to endoplasmic reticulum
## 382 GO:0034097 1.060742e-03  7.300805  0.7904288     5   40                                                     response to cytokine
## 391 GO:0000184 1.149301e-07  6.906737  2.4279734    14  116      nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
## 427 GO:0048872 5.312813e-04  6.664103  1.0322339     6   51                                           homeostasis of number of cells
## 431 GO:0019222 3.450419e-07  6.079087  3.1744111    15  204                                          regulation of metabolic process
## 446 GO:0006612 6.712822e-07  5.880000  2.7954574    14  134                                            protein targeting to membrane
## 472 GO:0016070 4.609505e-05  5.480509  2.1371868    10  127                                                    RNA metabolic process
## 520 GO:0019083 2.249698e-06  4.900293  3.5373061    15  169                                                      viral transcription
## 523 GO:0002181 2.629101e-03  4.749673  1.3977287     6   67                                                  cytoplasmic translation
## 593 GO:0006402 7.949142e-07  4.109288  5.6533465    20  272                                                   mRNA catabolic process
## 600 GO:0017148 5.978342e-03  3.961341  1.6486787     6   79                                       negative regulation of translation
## 622 GO:0051048 4.115504e-03  3.751466  2.0302881     7   97                                         negative regulation of secretion
## 623 GO:0051092 2.341978e-03  3.726496  2.3442502     8  112           positive regulation of NF-kappaB transcription factor activity
## 624 GO:0048519 4.037364e-05  3.685226  5.1369740    16  302                                negative regulation of biological process
## 625 GO:0001889 1.534560e-02  3.676923  1.4651564     5   70                                                        liver development
## 626 GO:0007050 8.467947e-03  3.660572  1.7728119     6   85                                                        cell cycle arrest
## 651 GO:1904950 5.140497e-03  3.590001  2.1140113     7  101             negative regulation of establishment of protein localization
## 652 GO:0048167 1.716174e-02  3.566260  1.5070180     5   72                                        regulation of synaptic plasticity
## 658 GO:0070498 1.014177e-02  3.511303  1.8419109     6   88                                 interleukin-1-mediated signaling pathway
## 664 GO:0007417 1.876509e-02  3.480645  1.5418219     5   75                                       central nervous system development
## 694 GO:0030522 2.193678e-02  3.331764  1.6045381     5   78                                 intracellular receptor signaling pathway
## 701 GO:0002262 1.413095e-02  3.248776  1.9789227     6   95                                                 myeloid cell homeostasis
## 711 GO:1905475 9.818627e-03  3.148615  2.3861118     7  114                           regulation of protein localization to membrane
## 736 GO:0051099 3.084855e-02  3.026011  1.7549759     5   84                                           positive regulation of binding
## 737 GO:0071216 7.936295e-03  2.994736  2.8675203     8  137                                     cellular response to biotic stimulus
## 738 GO:0051090 4.239697e-04  2.981419  5.5466634    15  265                  regulation of DNA-binding transcription factor activity
## 740 GO:1903039 5.370654e-03  2.968057  3.2652056     9  156                      positive regulation of leukocyte cell-cell adhesion
## 741 GO:0043484 2.074830e-02  2.962660  2.1558729     6  103                                               regulation of RNA splicing
## 773 GO:0032270 3.563571e-02  2.904003  1.8249319     5   95                positive regulation of cellular protein metabolic process
## 774 GO:0072657 5.601843e-04  2.899031  5.6993007    15  280                                         protein localization to membrane
## 776 GO:0033673 6.322052e-03  2.887952  3.3489288     9  160                                   negative regulation of kinase activity
## 780 GO:0043043 9.243884e-06  2.856679 10.8840187    27  520                                             peptide biosynthetic process
## 788 GO:0070304 4.171104e-02  2.771670  1.9047033     5   91 positive regulation of stress-activated protein kinase signaling cascade
## 809 GO:0045859 1.833423e-02  2.760109  2.6984127     7  136                                    regulation of protein kinase activity
## 810 GO:0034655 4.568297e-05  2.743696  9.9153903    24  475                         nucleobase-containing compound catabolic process
## 819 GO:0002221 2.062224e-02  2.689031  2.7628663     7  132                           pattern recognition receptor signaling pathway
## 821 GO:0090287 3.097210e-02  2.682357  2.3651810     6  113                regulation of cellular response to growth factor stimulus
## 823 GO:0070663 2.139719e-02  2.667348  2.7837971     7  133                                    regulation of leukocyte proliferation
## 851 GO:0043066 1.519838e-03  2.605183  6.2866146    15  306                                 negative regulation of apoptotic process
## 862 GO:0071559 4.259956e-02  2.471405  2.5535582     6  122                              response to transforming growth factor beta
## 870 GO:0002791 3.026418e-02  2.468841  2.9929060     7  144                                          regulation of peptide secretion
## 875 GO:0051251 1.700681e-02  2.428750  3.9331363     9  189                             positive regulation of lymphocyte activation
## 876 GO:0007283 1.705504e-02  2.427461  3.9349914     9  188                                                          spermatogenesis
## 881 GO:0045785 2.478269e-02  2.401180  3.5222732     8  171                                     positive regulation of cell adhesion
## 882 GO:0009617 5.977864e-03  2.374085  5.8815563    13  281                                                    response to bacterium
## 918 GO:0050867 1.559467e-02  2.338466  4.5419847    10  217                                   positive regulation of cell activation
## 922 GO:0060548 4.869073e-04  2.306653 11.5747353    24  553                                        negative regulation of cell death
## 924 GO:0000122 1.040857e-03  2.295477 10.0677173    21  481                negative regulation of transcription by RNA polymerase II
## 925 GO:0051338 5.836055e-04  2.274382 11.7212509    24  560                                       regulation of transferase activity
## 956 GO:0030098 2.983499e-02  2.186038  4.3391003     9  209                                               lymphocyte differentiation
## 960 GO:0045089 1.991976e-02  2.149117  5.4210786    11  259                            positive regulation of innate immune response
## 979 GO:0043207 3.042520e-03  2.122553 10.2560946    20  490                                     response to external biotic stimulus
## 982 GO:0045937 3.442067e-03  2.097738 10.3691242    20  496                       positive regulation of phosphate metabolic process
go_cell_type_filt_rbind <- map(go_cell_type_filt, function(l) {
  bind_rows(l, .id = "directions")
})
names(go_cell_type_filt_rbind) <- c("Monocyte", "T-cell", "NK", "B-cell")
# openxlsx::write.xlsx(go_cell_type_filt_rbind, file = "results/tables/go_pbmc_by_cell_type.xlsx")

# Plot
excel_path <- "results/tables/go_pbmc_by_cell_type.xlsx"
sheets <- excel_sheets(excel_path)
go_df_l <- purrr::map(sheets, ~ read_excel(excel_path, sheet = .x, col_names = TRUE))
names(go_df_l) <- sheets
go_terms <- c("GO:0007159", "GO:0001916", "GO:0031343", "GO:0050853")
go_terms_df <- purrr::map2(go_df_l, go_terms, function(df, term) {
  df[df$GOBPID == term, ]
})
go_df <- bind_rows(go_terms_df, .id = "cell_type")
go_terms_sorted <- c(
  "positive regulation of T cell mediated cytotoxicity", 
  "positive regulation of cell killing", 
  "leukocyte cell-cell adhesion", 
  "B cell receptor signaling pathway"
)
go_df$Term <- factor(go_df$Term, levels = rev(go_terms_sorted))
go_df$cell_type <- factor(
  go_df$cell_type,
  levels = c("T-cell", "NK", "Monocyte", "B-cell")
)
palette2 <- c("#c20a35", "#aa2edc", "#71bdd0", "#bbaa2a")
go_gg <- ggplot(go_df, aes(Term, -1 * log10(Pvalue), color = cell_type)) +
  geom_segment(aes(x = Term, xend = Term, y = 0, yend = -1 * log10(Pvalue))) +
  geom_point() +
  scale_color_manual(values = palette2) +
  labs(x = "", y = "-log10 (p-value)", color = "") +
  theme_light() +
  coord_flip()
go_gg

# saveRDS(go_gg, "results/R_objects/ggplots/lollipop_go_enrichment_by_celltype_pbmc.rds")

As we can see, there is a loss of function for each cell type.

6 Session Information

sessionInfo()
## R version 3.6.1 (2019-07-05)
## Platform: x86_64-apple-darwin15.6.0 (64-bit)
## Running under: macOS High Sierra 10.13.6
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/3.6/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] parallel  stats4    stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] forcats_0.5.0               stringr_1.4.0               dplyr_0.8.4                 purrr_0.3.3                 readr_1.3.1                 tidyr_1.0.2                 tibble_2.1.3                tidyverse_1.3.0             readxl_1.3.1                pheatmap_1.0.12             viridis_0.5.1               viridisLite_0.3.0           ggridges_0.5.2              ggrepel_0.8.1               topGO_2.38.1                SparseM_1.78                GO.db_3.10.0                GOstats_2.52.0              graph_1.64.0                Category_2.52.1             Matrix_1.2-18               GOplot_1.0.2                RColorBrewer_1.1-2          gridExtra_2.3               ggdendro_0.1-20             org.Hs.eg.db_3.10.0         AnnotationDbi_1.48.0        biomaRt_2.42.0              ggpubr_0.2.5                magrittr_1.5                Seurat_3.1.4                scran_1.14.6                scater_1.14.6               ggplot2_3.3.0               SingleCellExperiment_1.8.0  SummarizedExperiment_1.16.1 DelayedArray_0.12.2         BiocParallel_1.20.1         matrixStats_0.55.0          Biobase_2.46.0              GenomicRanges_1.38.0        GenomeInfoDb_1.22.0        
## [43] IRanges_2.20.2              S4Vectors_0.24.3            BiocGenerics_0.32.0         BiocStyle_2.14.4           
## 
## loaded via a namespace (and not attached):
##   [1] rappdirs_0.3.1           AnnotationForge_1.28.0   bit64_0.9-7              knitr_1.28               irlba_2.3.3              multcomp_1.4-12          data.table_1.12.8        RCurl_1.98-1.1           generics_0.0.2           metap_1.3                cowplot_1.0.0            TH.data_1.0-10           RSQLite_2.2.0            RANN_2.6.1               future_1.16.0            bit_1.1-15.2             mutoss_0.1-12            httpuv_1.5.2             xml2_1.2.2               lubridate_1.7.4          assertthat_0.2.1         xfun_0.12                hms_0.5.3                promises_1.1.0           evaluate_0.14            fansi_0.4.1              progress_1.2.2           caTools_1.18.0           dbplyr_1.4.2             Rgraphviz_2.30.0         igraph_1.2.4.2           DBI_1.1.0                htmlwidgets_1.5.1        RSpectra_0.16-0          crosstalk_1.0.0          backports_1.1.5          bookdown_0.18            annotate_1.64.0          gbRd_0.4-11              RcppParallel_4.4.4       vctrs_0.2.3              ROCR_1.0-7               withr_2.1.2              sctransform_0.2.1        prettyunits_1.1.1        mnormt_1.5-6             cluster_2.1.0           
##  [48] ape_5.3                  lazyeval_0.2.2           crayon_1.3.4             genefilter_1.68.0        edgeR_3.28.1             pkgconfig_2.0.3          labeling_0.3             nlme_3.1-145             vipor_0.4.5              rlang_0.4.5              globals_0.12.5           lifecycle_0.1.0          sandwich_2.5-1           BiocFileCache_1.10.2     modelr_0.1.6             rsvd_1.0.3               cellranger_1.1.0         lmtest_0.9-37            zoo_1.8-7                reprex_0.3.0             beeswarm_0.2.3           png_0.1-7                bitops_1.0-6             KernSmooth_2.23-16       blob_1.2.1               DelayedMatrixStats_1.8.0 ggsignif_0.6.0           scales_1.1.0             memoise_1.1.0            GSEABase_1.48.0          plyr_1.8.6               ica_1.0-2                gplots_3.0.3             bibtex_0.4.2.2           gdata_2.18.0             zlibbioc_1.32.0          compiler_3.6.1           lsei_1.2-0               dqrng_0.2.1              plotrix_3.7-7            fitdistrplus_1.0-14      cli_2.0.2                XVector_0.26.0           listenv_0.8.0            patchwork_1.0.0          pbapply_1.4-2            MASS_7.3-51.5           
##  [95] mgcv_1.8-31              tidyselect_1.0.0         stringi_1.4.6            yaml_2.2.1               BiocSingular_1.2.2       askpass_1.1              locfit_1.5-9.1           grid_3.6.1               tools_3.6.1              future.apply_1.4.0       rstudioapi_0.11          farver_2.0.3             Rtsne_0.15               digest_0.6.25            BiocManager_1.30.10      shiny_1.4.0              Rcpp_1.0.3               broom_0.5.5              later_1.0.0              RcppAnnoy_0.0.15         httr_1.4.1               npsurv_0.4-0             Rdpack_0.11-1            colorspace_1.4-1         rvest_0.3.5              XML_3.99-0.3             fs_1.3.2                 reticulate_1.14          splines_3.6.1            uwot_0.1.5               RBGL_1.62.1              statmod_1.4.34           sn_1.5-5                 multtest_2.42.0          plotly_4.9.2             xtable_1.8-4             jsonlite_1.6.1           R6_2.4.1                 TFisher_0.2.0            mime_0.9                 pillar_1.4.3             htmltools_0.4.0          fastmap_1.0.1            DT_0.12                  glue_1.3.1               BiocNeighbors_1.4.2      codetools_0.2-16        
## [142] tsne_0.1-3               mvtnorm_1.1-0            lattice_0.20-40          numDeriv_2016.8-1.1      curl_4.3                 ggbeeswarm_0.6.0         leiden_0.3.3             gtools_3.8.1             magick_2.3               openssl_1.4.1            survival_3.1-8           limma_3.42.2             rmarkdown_2.1            munsell_0.5.0            GenomeInfoDbData_1.2.2   haven_2.2.0              reshape2_1.4.3           gtable_0.3.0